Thomas Chalmers review (1975) has been a frequent citation for statement that vitamin C has no effects on the common cold.
by Harri Hemilš

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:

Hemilš 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.
  1. American Medical Association official statement in 1987
  2. Lancet editorial in 1979
  3. The US nutritional recommendations 1980 and 1989
  4. Major textbooks of infectious diseases
    1. Principles and Practice of Infectious Diseases (Mandell, Douglas, Bennett)
    2. Infectious Diseases: A Treatise of Infectious Processes (Hoeprich)
    3. Textbook of Pediatric Infectious Diseases (Feigin, Cherry)
  5. Textbooks on nutrition
    1. Human Nutrition in Health and Disease
    2. Nutrition, Concepts and Controversies
    3. Modern Nutrition in Health and Disease
    4. Other books on nutrition
  6. Major reviews of common cold treatment in journals:
  7. 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: Hemilš 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: Hemilš 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: Hemilš 2010