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Vitamin C for preventing and treating the common cold

RM Douglas EB Chalker B Treacy

DOI:10.1002/14651858.CD000980

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Roger Mann M.D.
Date received: November 25, 2008
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9896#9896

I would be interested in your results if you restricted studies to those using 1.0 grams or more.

Thanks
Roger
Sean Emerson
Date received: July 24, 2007
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9691#9691

Studies which find the effects of vitamin C on the common cold inconclusive invariably use less than 1g of ascorbic acid a day. Proponents of Vitamin C therapy consistently use 3 or more grams a day. This debate will not be resolved until both camps start testing the same dosages. Since the Ascorbic acid proponents acknowlege that <1g a day will have little therapeutic effect, it is incumbent on researchers to analyze the effect of megadoses.

I routinely dose to bowel tolerance. 0.5g every hour for eight hours will reach bowel tolerance for me. When I begin to become ill, I have dosed as high as 0.5g every 20 minutes without reaching bowel tolerance. I can significantly reduce the effect of a cold in this fashion, and once was the only one functioning in my office when everyone else was sick.

My rule of thumb is 35mg per pound of body weight per day. This must be distributed throughout the day to prevent overloading the ability of the stomach to absorb it, and to provide continuous saturation, because of the rapid decomposition of ascorbic acid once it is no longer in crystalline form. This dose is consistent with the levels of ascorbic acid produced by the liver of other mammals.
Dr Steve Hickey
Date received: July 10, 2005
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9423#9423

Vitamin C for preventing and treating the common cold

RM Douglas, EB Chalker, B Treacy
DOI:10.1002/14651858.CD000980

This paper by Hemila and Douglas is highly misleading. Two fundamental scientific errors invalidate the conclusions of their review.

Their first error is the dose range: the doses employed are too small. Treatment of disease requires pharmacological doses of vitamin C, in the range 10 ? 200g per day. [Cathcart, Medical Hypotheses, 7, 1359-76] Prevention of disease requires a minimum of 2.5g per day, in divided doses, to establish a dynamic flow through the body. In defending their review, Hemila and Douglas cite Levine [Levine et al. JAMA, 1999, 281,1415-23] as showing that the body is saturated by a dose of 0.5 g per day: this finding has been discredited. A more recent paper by Levine and colleagues shows that the body is not saturated by doses up to 18g per day. [ Padayatty et al, Ann Intern Med, 2004, 140, 533-7]. This discrepancy has been explained in a recent book. [Hickey and Roberts, Ascorbate, 2004, Lulu press].

The second error concerns the dose frequency. Since high doses of vitamin C have a half-life of about 30 minutes, single or twice daily doses do not increase plasma levels for more than a few hours. [Levine et al. JAMA 1999, 281,1415-23] Such doses provide a minimal protective effect. Given these infrequent doses, even a small positive effect implies a powerful therapeutic potential.

Douglas and Hemila have not shown that vitamin C is ineffective against the common cold, unless the doses used are both inadequate and inappropriate. They have, however, made clear that the previous 65 years of research has been based on a range of doses that are too small and too infrequent. Thus, the research to date may grossly underestimate the therapeutic value of vitamin C. Tests of appropriate dose levels and timing regimes are urgently required.

Steve Hickey PhD. Manchester Metropolitan University
Hilary Roberts PhD



Liz Dooley
Date received: September 24, 2004
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9310#9310

Plasma vitamin C level in healthy persons is saturated with doses less than 0.5 g/day (Levine et al. JAMA 1999;281:1415-23). Consequently, there is no basis to assume that doses substantially higher than 1 g/day would affect the incidence of colds when considering the negative findings of the large-scale trials (mostly 1 g/day). On the other hand, common cold infections change vitamin C metabolism so that vitamin C levels in leucocytes and in urine are reduced during colds (for review see Hemila: Br J Nutr 1992;67:3-16). Accordingly, it is quite possible that therapeutic supplementation during colds might show dose-dependency in the region above 1 g/day (Hemila: J Clin Epidemiol 1996;49:1079-87; Hemila: Med Hypotheses 1999;52:171-8). Nevertheless, our Cochrane review is limited to placebo-controlled trials, and in these trials the highest dose was "only" 6 g/day. There is such a great variability in the published trials so that comparing trials with different doses allows only hypothetical conclusions about dose-dependency. Furthermore, few of the trials examined therapeutic supplementation during common cold episodes, and those trials were mostly negative. Thus, the published trials do not give support nor do they dispute the possibility that therapeutic doses substantially higher than 1 g/day would be much more beneficial compared with 1 g/day.

Prof. Bob Douglas

Dr. Harri Hemilä

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


Liz Dooley
Date received: September 24, 2004
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9309#9309

Ludvigsson writes explicitly "Every class was divided at random into two groups." In our opinion this statement means that Ludvigsson was taking one class and he divided the subjects of that one class to two groups 'at random,' and then he went to another class and similarly randomized the second class. We disagree that cluster randomisation applied here.

As to the two small twin trials: Miller 1977 expicitly stated that "analysis of the paired comparisons?" so we conclude their SE values in their main table are based on paired t-test, event though this is not explicitly stated in their methods; Carr 1981 explicitly stated "the results for the six summary cold variables of the paired analyses of variance between active and placebo groups are shown?" so we conclude their P-values refer to paired analyses. In any case, the mean difference between the groups is the same whether we calculate difference of means or mean of paired differences. Failure to take into account the pairing of data would mean that we would be over-conservative in our estimate of the precision of any effect, but it is unlikely that this issue would anyway have influenced our conclusions in a meaningful way.

In the current review we have not used as an outcome variable mean symptom days per person but have concentrated on mean symptom days per episode.

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


Liz Dooley
Date received: September 24, 2004
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9308#9308

In the new edition of the review we have avoided this problem described above by combining all trial arms that were compared with the one placebo group into one trial arm for purposes of the meta-alysis

Prof Bob Douglas

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


Reuven Gilmore
Date received: July 26, 2004
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9273#9273

One gram daily is a small dose. Most mammals make 3 or more grams in their livers. Any practitioner of orthomolecular medicine knows that a minimum of several grams a day is needed to surely prevent a cold, and as much as 20 grams to cure one in progress. Not one trial in your RCT's qualifies.

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


Julian Higgins
Date received: February 29, 2004
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9196#9196

Further to David Wooff's comment, I suspect there may be other statistical flaws in this review that could be placed under the heading, 'unit of analysis errors'.

At least one study (Lugviggson) appears to be a cluster randomized trial, yet there is no discussion of the possible over-weighting of this study when naively included in the meta-analyses.

At least two studies appear to be twin studies (Carr and Miller). Should the matching be taken into account in the analysis, in a similar way to a simple cross-over trial?

The particular meta-analysis for 'Mean symptom days per person' in the comparison 'Vitamin C 1G daily or more vs placebo' worries me considerably. Of the six studies (10 contributions) included in this analysis, I suspect that at most two are free of unit of analysis errors of various kinds. This makes it a wonderful teaching example, but for the wrong reasons.

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


David Wooff
Date received: October 6, 2003
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9123#9123

There appear to be several instances where there is considerable overlap between studies, but they are treated as independent studies as far as the meta-analysis is concerned. For example, the Anderson 1974, 1974a, 1974b studies seem to be treated as independent in graph (comparison 01, outcome 04), but the control groups seem identical, and 275 people in the treatment group seem the same in each study. The effect is to inflate the value of this study. Indeed, the difference between the treatment groups for Anderson 1974a, 1974b (33 new people, *all* apparently with one or more respiratory episodes) raises further issues.

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.


Peggy Cruz
Date received: March 4, 2003
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9032#9032

I have always heard that Vitamin C was good for preventing colds. I have always made sure that I take my daily dose of multivitamins that have 100% USRDA value of all the essentials. I have always had at least 1 cold, maybe 2 every year. But for the past 3 years, whenever I feel the little tickle in my throat that more often than not signals the onset of a cold, I will take a megadose of vitamin C (more than 1000%USRDA). That day, I will sneeze and have a sinus headache. However, the next morning, my symptoms will have cleared up and I will be cold-free.

P. Cruz

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.