We are not entirely sure that Professor Patrick Holford of Teesside University and also Head of Science and Education at Biocare quite understands the purpose of issuing clarifications. Hint, the clue is in the name.
As it is impossible to comment on Holford’s page, we reproduce his clarifications here and address what is wrong with them. Here, we shall look at the vitamin C claim for colds.
Q [supposedly the BBC]. That in the same book, Chapter 24, still on the subject of vitamin C, Mr Holford cherry picks studies in order to back up his claims about the role of vitamin C in the treatment or prevention of colds. What is Mr Holford’s reasoning for using a retrospective analysis of data from studies carried out before 1974 only and ignoring the many studies that have taken place since?
A [Holford’s response]. “The referenced study used in the Optimum Nutrition Bible in relation to colds and vitamin C, was the most up-to-date systematic review of studies on vitamin C, published in 2000. The most recent systematic review of studies on vitamin C, published last year reaches more or less the same conclusions that Vitamin C supplementation reduces the duration of symptoms, reduces the severity of symptoms, but there is no convincing evidence on reducing incidence ie the number of colds. It reports that the strongest effect is for immediate high doses on the onset of a cold, for example if 8 grams is taken 46% of subjects have a cold for no more than a day. That is the equivalent of 176 oranges, hence the recommendation in the Optimum Nutrition Bible to supplement vitamin C in high doses when you have a cold. When the book is next updated I will cite this more recent review.
Holford Watch: No. This is wrong. Holford is confusing the wrong-headed text that he wrote in his book and the topic of this clarification. He muddies the water further, whether he understands this is a very different question.
A Cochrane Review: Vitamin C for preventing and treating the common cold (pdf) was available in 1998. It had been updated and revised in time for inclusion in the revision of New Optimum Nutrition Bible (NONB) in 2004. In NONB, Holford makes an unsubstantiated claim that there is a trial that shows vitamin C reduces the incidence of colds. This must have been a very remarkable trial to be thought worthy of off-setting the opinion of a systematic review of the topic, but we will never know, because he doesn’t provide a reference. The careful reader will know, however, that the Cochrane reviewers will have considered and maybe even included any such trial in their meta-analysis of the topic because that is how meta-analyses work. You find all of the studies and trials that sound relevant and you include the ones that meet some basic criteria (e.g., they were a fair test because they looked at dosages of 1g or more a day). The 1998 version included 30 trials (of “variable quality”). However, the 1998 Cochrane review of the topic, and the subsequent updates, all state that there is no evidence to support the role of vitamin C in reducing the incidence of colds.
Holford seems to accept this when he states:
The most recent systematic review of studies on vitamin C, published last year reaches more or less the same conclusions that Vitamin C supplementation reduces the duration of symptoms, reduces the severity of symptoms, but there is no convincing evidence on reducing incidence ie the number of colds. [Emphasis added.]
However, that is not what his books says; his book says that vitamin C reduces the incidence of colds.
The next part is a little tricky but Holford is being more than a tad disingenuous here. We are looking at the issue of whether vitamin C can treat colds; treat them in the sense of reducing their duration or the severity of their symptoms. If you consult NONB, you are referred to a paper that was not the “most up-to-date systematic review of studies on vitamin C, published in 2000”. The reader is referred to Vitamin C and the Common Cold: A Retrospective Analysis of Chalmers’ Review (pdf). This paper is a retrospective re-analysis of Chalmer’s 1975 review of trials: the authors did this because the Chalmer’s review is frequently-cited but has some serious flaws which they sought to correct (“fraught with errors and misleading data from the original studies”). The Chalmer’s 1975 review, the one that is being critiqued and reassessed was about 7 trials from a pool of 14; not the 37/38 that Holford claims in the book. Holford has either mis-reported this paper or provided the wrong reference.
It is beyond belief that Holford piously refers the reader to his version of what the latest Cochrane review of this topic says. Last year, in a September newsletter to his paying customers, Holford mangled the updated 2007 Cochrane Review to report some results that would have startled the authors. He took the 13.6% reduction in cold duration for children and claimed: “This equates to up to a month less ‘cold’ days per year for the average child”. What does your instinct tell you on this point without even engaging your mental arithmetic skills? Do you have a vague feeling that this would imply that these unfortunate children would have to experience more than 200 days of cold symptoms a year in order to experience a 13.6% reduction that amounts to “up to a month”? According to the review, children who had the highest number of colds might expect a reduction of 4 days per year. 4 days, nothing like a month. And, far from vindicating Holford’s recommendations, the Cochrane reviewers concluded: “The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use”.
So, Holford is not an adequate intermediary when it comes to interpreting evidence, but what did the Cochrane Review say about treating cold symptoms with vitamin C?
It reduced the duration and severity of common cold symptoms slightly, although the magnitude of the effect was so small its clinical usefulness is doubtful.
So, less than a ringing endorsement and it is clear that Holford is wrong about that. But what about his striking claim for the benefits of 8g of vitamin C per day?
It reports that the strongest effect is for immediate high doses on the onset of a cold, for example if 8 grams is taken 46% of subjects have a cold for no more than a day. That is the equivalent of 176 oranges, hence the recommendation in the Optimum Nutrition Bible to supplement vitamin C in high doses when you have a cold. When the book is next updated I will cite this more recent review.
No, that really isn’t all the review says and it almost beggars belief that anyone might think this. We will quote the review about the 1974 trial that mentions the dosage of 8g.
The statistically significant Anderson 1974e entry combined two different dosage arms. Anderson 1974e administered 4 g/day, and Anderson 1974f administered 8 g/day on the first day of illness only. The mean duration of illness episodes for those in the 4 g/day arm was 3.17 days, while that for 8 g/day arm was 2.86 days compared with the duration in the placebo group #4 of 3.52 days. This 1974 trial was bedeviled, however, by the fact that the investigators originally intended to compare results with two separate placebo groups. One of the placebo groups (#6) had substantial baseline differences when compared with the six vitamin C groups. The comparisons presented here are with the placebo group #4 that was much closer to the vitamin C groups with respect to baseline data (see Hemilä 2006a). If comparisons had been made with the placebo group #6 or a combination of the two placebo groups as the investigators had originally intended, the benefits would have been minimised as the mean episode duration for the placebo group #4 was 3.52, and for placebo group #6 was 2.83. Nevertheless, notwithstanding the placebo group problem, the proportion of ’short colds’, that lasted for only one day was larger in the 8 g/day group (46%; 222 out of 483) compared with the 4 g/day group (39%; 164 out of 417) (P = 0.046), consistent with the possibility of therapeutic benefit at the higher dosage (see p. 42 in Hemilä 2006a). [Emphasis added.]
The flaws in this study are obvious but note that the best that can be said is that the proportion of short colds is greater. The mean duration of the colds for the 8g/day group was 2.86 days. We just mention this because elsewhere Holford accuses others of suppressing relevant information:
“My suspicions proved correct. Having been accused of systematically misrepresenting scientific evidence, Goldacre and Professor of Pharmacology David Colquhoun, then referred to a Cochrane Systematic Review (the kind that they say is the best) on Vitamin C in colds saying that there was no evidence of a lesser incidence of colds . . . but failed to mention that the review concludes that Vitamin C reduces the severity and duration of symptoms. It also reports that the strongest effect is for immediate high doses on the onset of a cold, for example if 8 grams is taken 46% of subjects have a cold for no more than a day.”
And, you see, here, Holford neglects to mention that the mean duration is nonetheless 2.86 days, which, when you think about it, is rather rough on the people for whom this didn’t work – given how this must have altered the mean duration.
“When the book is next updated I will cite this more recent review.” The question is, will Holford cite it correctly and report it accurately? His citations are wrong and his assertions are wrong. Take the vitamin C for your cold, don’t take it, it’s your money. But please don’t be convinced into taking it by a supplements entrepreneur who cannot interpret research papers properly, report research accurately, nor handle simple arithmetic – when he is using those science, research skills and arithmetic to convince you that you ought to take it.
For more on Holford, vitamin C, colds and HIV/AIDS, see Gimpy’s post on The Pills ‘n’ Thrills & Bellyaches of Patrick Holford