Thomas Chalmers review
(1975) has been a frequent citation for statement that vitamin C has no
effects on the common cold.
by Harri Hemilä
Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
http://www.mv.helsinki.fi/home/hemila
Home page
http://www.mv.helsinki.fi/home/hemila/vitc_colds.htm
Papers on vitamin C and the common cold
Feb 6, 2014
In 1975 Thomas
Chalmers meta-analyzed 9 controlled trial on vitamin C and concluded that
there was no evidence of effect by vitamin C:
Chalmers
TC. Effects of ascorbic acid on the
common cold. An evaluation of the evidence.
Am
J Med 1975;58:532-6.
Published version: http://dx.doi.org/10.1016/0002-9343(75)90127-8
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/1092164
Scanned version:
BM
However,
the Chalmers 1975 review was shown to be erroneous in 1995:
Hemilä
H, Herman ZS. Vitamin C and the Common Cold: a Retrospective
Analysis of Chalmers' Review.
J
Am Coll Nutr 1995;14:116-123.
Published
version: http://dx.doi.org/10.1080/07315724.1995.10718483
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/7790685
Free
manuscript version:http://hdl.handle.net/10138/42358
Links
to references are added
Scanned
version: http://www.mv.helsinki.fi/home/hemila/H/HH_1995.pdf
See
also: http://www.mv.helsinki.fi/home/hemila/reviews/chalmers/
This
HTML document lists the monographs and journal papers which have
cited the Chalmers' 1975 review as an evidence that vitamin C has no
effect on colds.
- American
Medical Association official statement in 1987
- Lancet
editorial in 1979
- The
US nutritional recommendations 1980 and 1989
- Major
textbooks of infectious diseases
- Principles
and Practice of Infectious Diseases (Mandell,
Douglas, Bennett)
- Infectious
Diseases: A Treatise of Infectious Processes (Hoeprich)
- Textbook of Pediatric
Infectious Diseases (Feigin, Cherry)
- Textbooks
on nutrition
- Human
Nutrition in Health and Disease
- Nutrition,
Concepts and Controversies
-
Modern
Nutrition in Health and Disease
- Other
books on nutrition
- Major
reviews of common cold treatment in journals:
- Chalmers
(1975) as an example of important early important meta-analyses
American
Medical Association official statement in 1987
The
American Medical Association based its official statement that:
"One
of the most widely misused vitamins is ascorbic acid.
There is no
reliable evidence that large doses of ascorbic acid prevent colds or
shorten their duration"
wholly on Chalmers’ review
Council of Scientific Affairs, American Medical Association (1987)
Vitamin preparations as dietary supplements and as therapeutic
agents. JAMA
257:1929-36
Extract
Lancet
editorial in 1979
Lancet
referred to Chalmers’ meta-analysis in an editorial stating that
vitamin C has no worthwhile effect on the common cold
Editorial
(1979) Ascorbic acid: immunological effects and hazards.
Lancet
313:308
Comments
in: Pauling (1979) Ascorbic acid [letter]. Lancet
313:615
The
US nutritional recommendations 1980 and 1989
"Several reviewers
(Chalmers, 1975; Dykes and Meier, 1975) have concluded that any
benefits of large doses of ascorbic acid for these conditions are too
small to justify recommending routine intake of large amounts by the
entire population." (p.120 below)
Food
and Nutrition Board, National Research Council (1989)
Recommended
Dietary Allowances, 10th edn.
Washington
DC: National Academy Press Vitamin
C pp 115-25
p
120
"... several
reviewers (Chalmers, 1975; Dykes and Meier, 1975) believe that these
benefits of large doses of ascorbic acid are too
small to justify
recommending routine intake of large amounts by the entire population."
(p.77 below)
Food
and Nutrition Board, National Research Council (1980)
Recommended
Dietary Allowances, 9th edn.
Washington DC: National Academy of
Sciences Vitamin
C pp 72-82
Major
textbooks of infectious diseases
Principles
and Practice of Infectious Diseases (Mandell,
Douglas, Bennett)
Gwaltney
JM (2005)
The common cold.
In: Mandell, Douglas, and Bennett’s Principles and
Practice of Infectious Diseases, 6th edn [Mandell GL, Bennett JE,
Dolin R, eds]. Philadelphia: Elsevier Churchill Livingstone. pp
747-52
Gwaltney
JM (2000)The common cold.
In: Mandell, Douglas, and Bennett’s
Principles and
Practice of Infectious Diseases, 5th edn [Mandell GL, Bennett JE,
Dolin R, eds]. Philadelphia: Churchill Livingstone. pp 651-6
"Until truly
effective and specific treatment becomes available, there
will continue to be fads in the use of unproven remedies. The ingestion
of large doses of vitamin C has been widely used as a preventive or
therapeutic measure for colds. However, a careful analysis of the
studies has indicated that a placebo effect could not be ruled out.
Many participants correctly surmised from the taste of the contents of
the capsules used whether they were receiving vitamin C or placebo."
(This is Gwaltney's text in years from 1979 to 1995, referring only to
Chalmers 1975, see below the extracts)
Gwaltney
JM (1995)
The common cold.
In: Principles
and Practice of Infectious Diseases, 4th edn [Mandell GL, Bennett
JE, Dolin R, eds]. NY: Churchill Livingstone. pp 561-6
Gwaltney
JM (1990)
The common cold.
In: Principles
and Practice of Infectious Diseases, 3rd edn [Mandell GL, Douglas
RG, Bennett JE, eds]. NY: Churchill Livingstone. pp 489-93
Gwaltney
JM (1985)
The common cold.
In: Principles
and Practice of Infectious Diseases, 2nd edn [Mandell GL, Douglas
RG, Bennett JE, eds]. NY: Churchill Livingstone. pp 351-5
Gwaltney
JM (1979)
The common cold.
In: Principles
and Practice of Infectious Diseases, 1st edn [Mandell GL, Douglas
RG, Bennett JE, eds]. NY: Churchill Livingstone. pp 429-35
Infectious
Diseases: A Treatise of Infectious Processes (Hoeprich)
Liu
C (1994)
The common cold.
In: Infectious Diseases: A Treatise of Infectious
Processes, 5th edn [Hoeprich PD, Jordan MC, Ronald AR, eds].
Philadelphia, PA: Lippincott. pp 336-41
"There is no proof
of any curative value from the many proprietary remedies containing
vitamins {including vitamin C), bioflavinoids, multiple analgesics, or
antihistaminics in the treatment of the common cold." (This is
Liu's text in 1989, see below the extract)
Liu
C (1989)
The common cold.
In: Infectious Diseases: A Modern Treatise of
Infectious Processes, 4th edn [Hoeprich PD, Jordan MC, eds].
Philadelphia, PA: Lippincott. pp
288-93
Textbook of Pediatric
Infectious Diseases (Feigin, Cherry)
Dick
EC, Inhorn SL
Rhinoviruses.
In: Textbook of Pediatric Infectious Diseases, 3rd edn
[Feigin RD, Cherry JD, eds]. Philadelphia, PA: Saunders. pp 1507-32
Dick EC, Inhorn SL, Glezen WP (1998) Rhinoviruses.
In: Textbook
of
Pediatric Infectious Diseases, 4th edn [Feigin RD, Cherry JD, eds].
Philadelphia, PA: Saunders. pp 1839-65
Textbooks
on nutrition
Human
Nutrition in Health and Disease
"Chalmers (1975)
carried out a similar analysis of 14 clinical trials and reported that
severity of symptoms was significantly worse in patients who received
the placebo. Unfortunately, many volunteers correctly guessed their
treatment and when this was taken into account, differences in both the
number and severity of colds were minor and insignificant."
(Thurnham 2000 p. 256 below)
Thurnham
DI, Bender DA, Scott J (2000) Water-soluble vitamins.
In:
Human Nutrition and Dietetics, 10th edn [Garrow JS, James WPT, Ralph
A, eds]. London: Churchill Livingstone. pp
249-87
"... claiming that
large daily doses of vitamin C reduced the likelihood of contracting
the common cold. The popularity of this concept prompted at least
14 clinical trials, which failed to show an effect of vitamin C
(Chalmers 1975)" (Halsted 1993, p. 241 below)
Halsted
CH (1993) Water-soluble vitamins.
In: Human Nutrition and
Dietetics, 9th edn [Garrow JS, James WPT, eds]. London: Churchill
Livingstone. pp
239-63
Nutrition,
Concepts and Controversies
"... in 1975 a
physician [Chalmers] reviewed many of them. He found that,
statistically, takers of vitamin C did indeed suffer fewer and milder
colds than takers of placebos. The difference averaged one-tenth of one
cold per year, and one tenth of one day per cold in favor of the
vitamin C-takers. While such a measurable difference is cause for great
excitement among laboratory scientists, a person hearing about it
wouldn't think the gain worth considering." (Hamilton 1994, p.
404 below)
Hamilton
EMN, Whitney EN (1994)
Nutrition, Concepts and Controversies, 6th edn. NY: West Publ. pp
403-29
"...
double-blinded studies on vitamin C and colds... A pooling of the data
from eight of these showed that there was a
difference of a
tenth of a cold per year and an average difference in duration of a
tenth of a day per cold in those subjects taking vitamin C
over those taking
the placebo [ref. to Chalmers]." (Hamilton
1982, p. 278 below)
Hamilton
EMN, Whitney EN (1982)
Nutrition, Concepts and Controversies, 2nd edn. NY: West Publ. pp
277-93
Modern
Nutrition in Health and Disease
"The use of
megadoses of vitamin C to prevent the common upper respiratory diseases
remains an unproven claim. Fourteen studies have been reviewed of which
eight were considered acceptable [ref to Chalmers]. Only minor and
insignificant effects were noted in terms of the prophylactic benefit
of administering megadoses of vitamin C." (Shils et al. 1994, p.
652, see below)
Shils
ME, Olson JA, Shike M, eds (1994) Modern Nutrition in Health
and Disease, 8th edn. Malvern, PA: Lea & Febiger. pp
652-61
Other
books on nutrition
Whitney
EN, Rolfes SR (1993) Understanding Nutrition. St Paul, MN:
West Publ. pp 332-5
Major
reviews of common cold treatment in journals
"The placebo
effect in the treatment of colds was first shown >70 years ago and
has since been demonstrated in subsequent studies [ref. to Chalmers
1975]." (p.572 below)
Caruso TJ, Prober CG, Gwaltney JM Jr (2007) Treatment of Naturally
Acquired Common Colds with Zinc: A Structured Review. Clin
Infect Dis 45:569-574
Comments
in: Hemilä 2013
Thus, Caruso and Gwaltney kept referring to Chalmers (1975), even
though they knew that it was flawed, since they read and replied to my
comment on their 2005 paper, see below.
"Chalmers [1975] showed the extent to which curious subjects will go to
unblind themselves. He described a study that initially showed a
positive therapeutic effect of capsules containing vitamin C on the
common cold. However, blinding was not maintained, because many
subjects bit through the capsules to taste the contents, which they
correctly identified. When data from the unblinded subjects were
discarded, “there were no differences in the durations of colds”
(p.810 below)
Caruso
TJ, Gwaltney JM Jr (2005) Treatment of the common cold with
echinacea: a structured review. Clin
Infect Dis 40:807-10
Comments
in: Hemilä 2005a
Lorber
B (1996) The common cold. J Gen Intern Med 11:229-36
"One clinical
trial of ascorbic acid showed that the apparent benefit in the vitamin
C recipients was accounted for by volunteers who had tasted the
contents of their capsules and correctly identified the treatment.
Reanalysis with omission of these subjects found no evidence of a
treatment benefit [ref. to Chalmers]" (p.410, see below)
Sperber
SJ, Hayden FG (1988) Chemotherapy of rhinovirus colds.
Antimicrob
Agents Chemother 32:409-19
Steele
RW (1988) Antiviral agents for respiratory infections. Pediatr
Infect Dis J 7:457-61
Anderson
LJ, Patriarca PA, Hierholzer JC, Noble GR (1983) Viral
respiratory illnesses. Med Clin North Am 67:1009-30
Hirsch
MS, Swartz MN (1980) Antiviral agents. Part II. N Engl J Med
302:949-53
Chalmers
(1975) as an example of important early important meta-analyses
A list "To
illustrate the evolution of fair tests of treatments, the James Lind
Library also contains images of key passages from manuscripts, books,
journal articles and other relevant material" gives the Chalmers
(1975) review as one example:
"Chalmers
TC (1975). Effects of ascorbic acid on the common cold. An
evaluation of the evidence. Amer J Med 58:532-6. "
JamesLindLibrary.org
(2014)
"Box 1. Early
Systematic Reviews of the Effects of Health Care Interventions:
Chalmers TC (1975) Effects of ascorbic acid on the common cold. An
evaluation of the evidence. Am J Med 58: 532-536." (Chalmers
study is the second earliest meta-analysis listed, p. 3 see below)
Bastian H, Glasziou P, Chalmers I (2010)
Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We
Ever Keep Up? PLoS Med 7(9): e1000326.
Comments in: Hemilä
2010