... 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 Feinman, 1985
“Surely You're Joking, Mr.
Feinman”
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 Feinman, 1988
“What Do You Care What Other
People Think?”
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
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
… Where I
have been
necessarily led, in this disagreeable part of the work, to criticise
the sentiments of eminent and learned authors, I have not done it with
a malignant view of depreciating their labours, or their names; but
from a regard to truth, and to the good of mankind. I hope such motives
will, to the candid, and to the most judicious, be a sufficient apology
for the liberties I have assumed.
James Lind, 1753
A Treatise of the Scurvy
The status of an ‘expert’ implies that an
individual is thoroughly familiar with the particular field.
Unfortunately, in the vitamin C field, the track record of many experts
is poor.
Nutritional authorities
James A Olson,
Robert E Hodges,
and Victor Herbert
(see Safety)
were
all members of the first committee preparing the 10th edition of
the US RDA nutritional recommendations, which plays a central role in
US governmental policy, and indirectly affects policy in numerous other
counties (FNB 1989a).
James
A. Olson was also an editor of a major textbook on
nutrition (Shils, Olson, et al. 1994, 1999). The review of vitamin C by
Olson and Hodges (1987),
which contained the anecdotal stories of
vitamin C toxicity (see Safety),
was planned as the
vitamin C section of the 10th edition of the RDA recommendations (Olson
1986; Pellett 1988). The US National Academy of Sciences decided,
however, not to publish the RDA draft by the first committee because of
an impasse resulting from scientific differences of opinion between the
first committee and the scientific reviewers appointed by the National
Academy of Sciences (Press 1985;
Marshall
1985). One reason for the
disagreements was the proposal that the RDA level for vitamin C
recommendation be lowered from 60 mg/day to 40 mg/day for men and 30
mg/day for women. The second RDA committee kept the vitamin C level at
60 mg/day for both men and women (FNB 1989a).
Victor Herbert, who reiterated the anecdotal stories of vitamin C
toxicity (see Safety)
in
one of his papers (Herbert
1993), was also a member of the committee preparing the 9th edition of
the US RDA nutritional recommendations (FNB
1980). Herbert received the
1972 McCollum Award for outstanding scientific accomplishment in the
field of nutrition (Anonymous 1973),
and
was the president of the American Society for Clinical
Nutrition in 1980-1981. In 1984 Herbert received the FDA
Commissioner’s Special Citation Award for "outstanding and
consistent contributions against the proliferation of nutrition
quackery to the American consumer" (Halsted 2003;
Oransky 2003: Scott 2004).
In his
reminiscences Pauling described an acrimonious exchange of letters with
Victor Herbert who rejected the results of all placebo-controlled
trials on vitamin C and the common cold without any reasonable
argument. Pauling commented that "I finally became sufficiently
irritated by this fellow that I decided I ought to do something about
it. So I sat down one summer and in two months wrote a book, Vitamin C
and the Common Cold " (Marinacci 1995
pp
248-51). In this respect
Herbert was, paradoxically, indirectly behind the increase in the
popular enthusiasm for vitamin C supplementation that resulted from
Pauling’s book. The current author pointed out
that Herbert’s conclusions (1993),
that
there is no reliable
data to show that vitamin C supplementation may provide any benefit and
that vitamin C supplements may instead be highly harmful, were based on
a grossly biased selection of references (Hemilä 1994b).
Stephen Barrett (2007)
has written several books on nutritional
quackery (Barrett 1980; Barrett & Herbert 1994), and received
the FDA Commissioner’s Special Citation in 1984 for
"outstanding and consistent contributions against the proliferation of
nutrition quackery to the American consumer." Barrett also received the
2001 Distinguished Service to Health Education Award from the American
Association for Health Education. However, Barrett’s
presentation of facts related to the findings from studies on vitamin C
and the common cold have been markedly biased. In a comment on
Barrett’s paper (1995)
claiming
there is no evidence that
vitamin C might affect colds, Hemilä (1995b)
pointed
out that
"Anderson et al. (1972)
found
that vitamin C supplementation (1-4 g/
day) decreased the ‘numbers of days confined to
house’ per subject by 48% in subjects with a low dietary
intake of fruit juices [see Hemilä 2006
Table 13, p 35]. Barrett’s claim that
at best there is only a slight reduction in symptoms appears grossly
misleading considering the published results." Stephen Barrett replied
to this that "Anderson’s first study found … a 30%
difference." In a subsequent letter Edgar Villchur (1995)
pointed
out
that "Barrett’s reply in the same issue challenges
Hemilä’s reporting accuracy, but Hemilä is
correct … Barrett, however, doesn’t say he is
citing a different part of the Anderson data, and thus makes it seem
that Hemilä has either misread or misrepresented Anderson." In
a reply to this accusation, Stephen Barrett (1995)
conceded
that "Villchur is
correct that Hemilä and I referred to different figures."
Experts
in clinical trials, systematic reviews and nutrition
Thomas Chalmers, Paul
Meier, A.
Steward Truswell, and Jos
Kleijnen are
experts in controlled trials, medical statistics, nutrition, and
systematic reviews, yet their reviews on vitamin C and the common cold
contain lots of factual errors and misleading statements (see
Hemilä 2006
pp
36-45; problems
in
reviews). The Chalmers (1975)
and Dykes and Meier (1975)
reviews
were
cited in major textbooks of infectious diseases and in the US RDA
recommendations, although some of the numerous shortcomings of both
reviews should have been apparent to any expert even superficially
familiar with the original study reports.
US
nutritional recommendations
In the most recent US nutritional recommendations (FNB 2000 pp
126-7),
Chalmers’ review (1975)
and the Hemilä and Herman
criticism (1995;
see
Criticism)
of
Chalmers’ review are cited in the same
paragraph without mentioning that the latter paper shows that the
former review is invalid. Thus, the experts writing the vitamin C
chapter did not read or understand the two papers cited to see that
they were incompatible. Although the most recent recommendations
extensively discuss the observational studies related to the
possibility that vitamin C intake might affect chronic diseases, the
recommendations ignore some 40 placebo-controlled trials that have
examined the preventive effect of vitamin C on colds (FNB 2000 p
117,
p
127; Douglas, Hemilä, et al. 2007).
Only 4 controlled trials are cited
in the US
recommendations (Peters et al. 1993;
Coulehan et al. 1976;
Miller
et
al. 1977;
Ludvigsson
et al. 1977).
Since
the Ludvigsson et al. trial
(1977)
mentioned
in the
recommendationsis is only one of the 6 largest
(Hemilä 1997) ,
83%
(5/6) of the largest common cold trials are simply
ignored, and some 90% of all the placebo-controlled trials on vitamin C
and the common cold are ignored in the current US nutritional
recommendations.
Even in the case of the Ludvigsson paper (1977),
the
study findings are
disregarded in the recommendations (FNB 2000 p
127). Ludvigsson et al.
(1977)
found
a 14% reduction (P = 0.008) in the duration of
‘absence from school because of upper respiratory tract
infection’ in the main trial, and a 39% reduction (P = 0.002)
in the duration of ‘upper respiratory tract
infection’ in the smaller trial, but these findings are not
mentioned in the recommendations. Two large trials reporting that
vitamin C supplementation significantly increased the proportion of
participants who remained free of illness during supplementation
(Hemilä 2006
Table
20, p 44) are not cited in the recommendations either, or any of the UK
trials that found a significant proportion of participants benefiting
when the outcome is ≥2 colds during the trial
(Hemilä 2006
Table 22, p 47).
Neither were any of the 3 trials that found a significant reduction in
pneumonia incidence by vitamin C supplementation
(Hemilä 1997;
Hemilä
and Louhiala 2007)
mentioned
in
the recommendations. It is not clear to what extent the poor
coverage of literature is caused by lack of knowledge of the studies,
and how much by an intentional decision to discard studies that do not
fit with a preconception that vitamin C is useless for colds and other
respiratory infections.
In systematic reviews it is essential to cover the published studies
widely and analyze the results objectively (Ian Chalmers &
Altman 1995;
Higgins
& Green 2006),
but
this was not done in
the most recent US nutritional recommendations (FNB 2000).
Although the
common cold trials do not allow explicit conclusions to be drawn about
what might be the best doses of vitamin C intake, the published trials
do show that large doses affect common cold severity and duration in
large groups of people, and the incidence of colds in some people.
Objective discussion of the common cold trials also provides
justification to carry out further study, and to use susceptibility to
and severity of infections as potential outcomes of interest in
considering the ‘optimal intake levels’ instead of
focusing only on cancers and cardiovascular diseases, and using
‘maximal neutrophil concentration with minimal urinary
loss’ as a surrogate with no established validity against
clinically relevant outcomes.
The problems of expert reliability in nutritional recommendations are
also seen in other vitamin C issues. In the 10th edition of RDA,
comments on vitamin C and cholesterol metabolism were based on 2 trials
that did not use placebo-control (FNB 1989a pp
120-1), and 3
placebo-controlled studies which found a significant decrease in
elevated cholesterol levels with vitamin C supplementation were
disregarded (Hemilä 1992c,
1993).
UK
nutritional recommendations
Similar problems are faced in the UK nutritional recommendations (DH
1991
[see Hemilä 1997d]),
where
no mention is made of the
possible role of vitamin C on the common cold, although some 40
placebo-controlled trials have been carried out. Furthermore, one of
the trials cited in the UK recommendations did report that the
geometric mean duration of colds was 6.4 days in vitamin C-deprived
subjects and 3.3 days in non-deprived subjects. The authors concluded
that "Such evidence as there is, however, definitely confirms the
hypothesis that the absence of vitamin C tended to cause colds to last
longer" (Bartley, Krebs & O’Brien 1953 p
43), but the
authors of the UK recommendations disregarded this (DH 1991).
The
brief
discussion of the vitamin C and cholesterol issue referred to a single
uncontrolled intervention study, and disregarded 11 published
placebo-controlled trials (DH 1991;
Hemilä
1992c,
1997d).
Textbooks
of infectious diseases
In the most recent editions of Mandell et al.’s textbook of
infectious diseases (Gwaltney 2000, 2005), Chalmers’ review
(1975)
is no longer cited; however, comments on vitamin C and the
common cold are based on 2 small trials with artificially inoculated
colds (Walker et al. 1967;
Schwartz
et al. 1973).
These
2 trials
recorded only 36 and 21 common cold episodes respectively, whereas none
of the 5 large-scale trials recording over 1,000 natural common cold
episodes per trial (Hemilä 2006:
Table
14) is cited (Gwaltney 2000, 2005). In a
classic paper, Thomas Chalmers pointed out that negative findings from
small trials may correspond to the type II error in statistics and
concluded that "Concern for the probability of missing an important
therapeutic improvement because of small sample sizes deserves more
attention in the planning of clinical trials" (Freiman et al. 1979).
Thus, drawing conclusions from trials with 36 and 21 common cold
episodes may lead to a false negative conclusion. Furthermore, it is
possible that natural colds differ from artificially induced colds. The
rate of the former is about 1 per year or 0.02 per week for adults,
whereas the rate of the latter was 0.4 to 1.0 per week (Walker et al.
1967;
Schwartz
et al. 1973),
indicating
that the exposure level to
viruses was orders of magnitude higher in the artificially inoculated
colds, which may affect the role of vitamin C.
Bias
against vitamin C
Pauling (1971b,
1976a
pp 121-38, 1986a pp 225-36) also provided several
examples of how the authorities in nutrition misinterpreted and ignored
the findings of published trials. Evidently, a personal problem for
Pauling was that "Medical experts have a long history of resisting
scientific innovations from what they define as ‘the
outside’ " (Barber 1961).
The poor quality of expert comments on vitamin C and the common cold is
puzzling. Goodwin and Tangum (1998)
provided several examples to
support the conclusion that there has been systematic bias against the
concept that vitamins might be beneficial in levels higher than the
minimum required to avoid classic deficiency diseases: "Throughout much
of the 20th century, American academic medicine was resistant to the
concept that micronutrient supplementation might prove beneficial. This
resistance is evident in several ways: (1) by uncritical acceptance of
bad news about micronutrient supplements; reports of toxic effects were
rarely questioned and widely quoted; (2) by the scornful, dismissive
tone of the discussions about micronutrient supplementation in
textbooks of medicine, a tone avoided in most medical controversies;
and (3) by the skeptical reaction greeting any claim of efficacy of a
micronutrient, relative to other therapies; indeed, most claims were
simply ignored."
Bias against vitamin C was also documented by Richards (1988, 1991;
Galloway 1991; Huxtable 1992; Segerstråle 1992) who compared
the attitudes and arguments of physicians to three putative cancer
medicines: 5-fluorouracil, interferon, and vitamin C.
The evaluation of the potential effectiveness of a therapeutic method
usually depends greatly on the possibility of biologically
rationalizing the method. Goodwin and Goodwin (1981, 1984)
reviewed
several
cases in which an effective method of treatment was erroneously
rejected due to a lack of understanding of the physiological mechanism
of the effect. They designated this problem ‘the tomato
effect’, since the tomato was considered poisonous in the USA
in the 1700s because several other plants in the same family were
poisonous: "The tomato effect in medicine occurs when an efficacious
treatment for a certain disease is ignored because it does not
‘make sense’ in the light of accepted theories of
disease mechanism and drug action." Thus, the question of evaluating a
new method of therapy is not just whether a moderate effect is
reproducible in controlled trials, but substantially depends on
conceptual issues related to the biological explanations (Vandenbroucke
1998a; Vandenbroucke & de Craen 2001).
It is possible, for
example, that the claim in the biochemistry textbooks that vitamin C
participates in the hydroxylation of proline in collagen (Berg et al.
2002) leads to a misleading impression of the mechanism of vitamin C
action, as the effects of vitamin C on other biochemical reactions
(Englard & Seifter 1986; Padh 1990) and on the immune system
(Hemilä 1997a,
2003a)
are not mentioned at all. Some further
possible conceptual reasons for the bias against the effects of vitamin
C on common cold have been discussed elsewhere (Hemilä 1996a,
1997a).
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main text should be freely accessible at least as an abstract, but some
links
below require a permission from publisher for any access.
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