eMJA: Megadose vitamin C in treatment of the common cold: a randomised controlled trial

Letters

Megadose vitamin C in treatment of the common cold: a randomised controlled trial

Luis Vitetta, Avni Sali, Bill Paspaliaris and Nicola J Reavley

MJA 2002; 176 (5): 298-299

To the Editor: There is much conflicting evidence that increased intake of vitamin C enhances the natural protective mechanisms of the body and decreases both the incidence and severity of the common cold.1

It is regrettable that the study by Audera and colleagues failed to show a significant therapeutic effect of megadose vitamin C in treatment of the common cold.2 The groups compared had, on average, similar composition after randomisation. However, the viral infections that cause the common cold and its progression to ill health, as evidenced by multiple symptoms, are affected by many factors, while symptom severity is well known to vary greatly. Therefore, the study's reliance on respondents' self-diagnosis of symptom severity and onset is a significant weakness in design.

Randomisation of participants to the treatment groups may have been insufficient to override this design deficit, thereby significantly biasing the outcome. A better design might have combined patient self-report of symptom severity with physical examination, thus allowing independent and professional assessment of severity. Also, proper assessment of previous history of severity of cold symptoms is crucial for proper randomisation to treatment groups. If Audera and colleagues' study failed to control for this history, then randomisation may have also failed to balance its effect equally between treatment groups, significantly compromising the study's validity to detect any therapeutic benefit of vitamin C. Cold symptoms also vary diurnally, while severity varies with alcohol use and smoking status,3,4 which also affect vitamin C absorption.5,6 No information was provided on study participants' alcohol consumption and smoking status.

Finally, the study did not assess stress, which may constitute a further, important uncontrolled bias. A recent cohort study of stress and the common cold concluded that all four dimensions of stress investigated — stressful life events, negative affects, positive affects and perceived stress — were significantly related to occurrence of the common cold.7 Stress may also have significantly affected symptom severity and participants' perception of their symptoms.

Certainly, the trend observed in the placebo group of shorter duration of some symptoms and lower mean severity could have been due to less severe symptom history, compounded by a lower degree of overall stress.

Douglas RM, Chalker EB, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2000; 2: CD000980. <PubMed>
Audera C, Patulny RV, Sander BH, Douglas RM. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. Med J Aust 2001; 175: 359-362. <eMJA full text> <PubMed>
Smith A, Tyrrell D, Coyle K, et al. Diurnal variation in the symptoms of colds and influenza. Chronobiol Int 1988; 5: 411-416. <PubMed>
Cohen S, Tyrrell DA, Russell MA, et al. Smoking, alcohol consumption, and susceptibility to the common cold. Am J Public Health 1993; 83: 1277-1283. <PubMed>
Pamuk E, Byers T, Coates R, et al. Effect of smoking on serum nutrient concentrations in African–American women. Am J Clin Nutr 1994; 59: 891-895. <PubMed>
Kleszczewski T, Kleszczewska E. FIA of vitamin C in blood serum in humans at increasing ethanol concentration. J Pharm Biomed Anal 2001; 25: 477-481. <PubMed>
Takkouche B, Regueira C, Gestal-Otero JJ. A cohort study of stress and the common cold. Epidemiology 2001; 12: 345-349. <PubMed>

(Received 15 Oct 2001, accepted 26 Nov 2001)

Graduate School of Integrative Medicine, Swinburne University Of Technology, Melbourne, VIC.

Luis Vitetta, Director of Research; Avni Sali, Professor and Head of School; Bill Paspaliaris, Senior Research Fellow; Nicola J Reavley, Research Assistant.

Correspondence: Dr L Vitetta, Graduate School of Integrative Medicine, Swinburne University of Technology, 9 Frederick St, Hawthorn, VIC 3122. LVitettaATmedicine.swin.edu.au

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In reply: Precisely because of the temporal variation in symptom severity described by Vitetta and colleagues, we judged that medical professionals are not as well able, in a variably timed interview, to quantify patients' cold symptoms as the patients themselves can do on a continuing basis. Therefore, we consider that our study1 would have been no more valid if the detailed symptom severity cards had been supplemented by one or more physical examinations. In that respect, we are in good company with others who have studied the common cold over many years.2

We agree that double-blind randomisation does not necessarily distribute all relevant variables equally. That is why, in Box 2 of our study report, we presented four variables — age, sex, mean number of colds in the previous year, and mean number of days unwell with colds in the previous year.1 The likelihood that stress, smoking and alcohol status would have been sufficiently maldistributed in this large group to mask a significantly beneficial effect in even one of the three groups which received high-dose vitamin C seems vanishingly small. Nevertheless, we acknowledge that the study would have been stronger if we could have reported the distribution of these three potential confounders.

We contest the view of Vitetta and colleagues that the evidence from randomised controlled trials of vitamin C in treating the common cold conflicts significantly (see Box 1 of our article1). The overview finding — that mega-doses of vitamin C for prophylaxis produce a relatively trivial reduction in cold severity but no reduction in incidence3 — was the stimulus for our own study. No community studies of this issue have been flawless, but the mounting collective evidence suggests that we should look elsewhere for a cold panacea.