Letter to the Editor Randomised trials on vitamin C

Lykkesfeldt and Poulsen’s review has a promising title, and in the introductory paragraph, they state that ‘over the years, it has been suggested that vitamin C be used as a remedy against many diseases as different as common colds and cancers’. Given their title and introduction, one would expect a discussion about randomised controlled trials (RCT) on vitamin C and the common cold. However, this topic is ignored in their review. This is an unfortunate omission because the common cold studies give interesting information on the issues that Lykkesfeldt and Poulsen discuss. We have written a Cochrane review on vitamin C and the common cold. We identified twenty-nine placebocontrolled comparisons on the effect of regular vitamin C supplementation on common cold incidence, twenty-nine comparisons on regular vitamin C and common cold duration and seven comparisons on therapeutic vitamin C and common cold duration. Most of the included trials were RCT, although that was not our inclusion criterion. In our Cochrane review, we found significant heterogeneity in the effect of vitamin C on common cold incidence. In five RCT with participants under heavy acute physical stress – three of them with marathon runners – vitamin C halved the incidence of colds. Lykkesfeldt and Poulsen suggest that RCT on vitamin C have been negative because the dietary vitamin C intake of participants has been high. However, there is no basis for assuming that the benefit of vitamin C for physically stressed participants is caused by low dietary vitamin C intake. In particular, Peters et al. estimated that the marathon runners in their trial had a high level of dietary vitamin C intake, on average 0·5 g/d, yet 0·6 g/d vitamin C supplementation still reduced the incidence of colds. This refutes Lykkesfeldt and Poulsen’s proposal that vitamin C cannot be beneficial if dietary vitamin C intake is high: ‘we believe that it is imperative that enrolled subjects have hypovitaminosis C at study entry and that this condition is used as an entry-level inclusion criterion in order to ensure a possibility of effect’ (p. 1256). Under some conditions, additional vitamin C may be beneficial even in the case of high dietary vitamin C intake. Lykkesfeldt and Poulsen also state that ‘it is striking that no study has used vitamin C deficiency as an inclusion criterion’ (p. 1256), which is misleading. In this journal, I reported a systematic review on vitamin C and common cold incidence, which was restricted to trials carried out in the UK. The rationale for including only UK trials was that several surveys in the 1970s and earlier had found a particularly low dietary vitamin C intake in the UK. Thus, my restriction to the UK trials served as a surrogate for low dietary vitamin C intake. In one of the identified trials, the authors estimated that the average dietary vitamin C intake was 10–15 mg/d, in another trial, it was 50 mg/d, and in a third trial, the authors noted that the average intake in the UK was 44 mg/d, without estimating the intake of their own participants. In four trials with UK males, vitamin C supplementation reduced common cold incidence by 30 % (rate ratio 0·70; 95 % CI 0·60–0·81), whereas in four trials with females, it had no effect (95 % CI 0·86–1·04). The strongest evidence for vitamin C and sex interaction was seen in the RCT by Baird et al.. Low-dose vitamin C supplementation, 0·08 g/d, decreased the incidence of colds by 37 % in males but had no effect on females (test for vitamin C and sex interaction P1⁄40·0001). Furthermore, Tyrrell et al. found in a therapeutic RCT in the UK that vitamin C significantly reduced the number of recurrent colds in males but not in females, although the interaction was NS. Thus, trials carried out in the UK in the 1970s and earlier are interesting for the question of whether vitamin C supplementation might be beneficial for people with rather low dietary vitamin C intake. The UK studies on the common cold suggest that there may be a vitamin C and sex interaction when dietary vitamin C intake is rather low. Vitamin C has also reduced the duration of colds. In regular supplementation trials, $0·2 g/d vitamin C shortened the mean duration of colds in adults by 8 % and in children by 13 %. The largest RCT with adults was performed by Anderson et al., and it found a 21 % decrease in the number of days confined indoors per episode (P1⁄40·015) with the dosage of 1 g/d each day and 3 g/d extra for 3 d when the participant caught the common cold. The largest RCT with children was by Ludvigsson et al. who found a 14 % decrease per episode in absence from school because of the common cold by using 1 g/d (P1⁄40·016). The effect of vitamin C on the duration of colds is not restricted to people with low dietary vitamin C intake. Furthermore, there is British Journal of Nutrition (2011), 105, 485–487 q The Author 2010