Vitamin C for preventing and treating the common coldVITAMIN C FOR PREVENTING AND TREATING THE COMMON COLDDouglas RM, Hemila H, D'Souza R, Chalker EB, Treacy BDate of most recent amendment: 06 July 2004Date of most recent substantive amendment: 10 August 2004This record should be cited as: Douglas RM, Hemila H, D'Souza R, Chalker EB, Treacy B. Vitamin C forpreventing and treating the common cold. The Cochrane Database of Systematic Reviews 2004, Issue4. Art. No.: CD000980.pub2. DOI: 10.1002/14651858.CD000980.pub2.ABSTRACTBackgroundThe role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment.ObjectivesTo discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms.Search StrategyThis updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004).Selection CriteriaPapers were excluded if a dose less than 200 mg daily of vitamin C was used; if there wasno placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment. Data collection and analysisTwo reviewers independently extracted data and assessed trial quality. 'Incidence' of coldsduring prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores. Main ResultsTwenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooledRR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). 1Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis . A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen trial comparisons that involved 7,045 respiratory episodes contributed to the meta-analysis of severity of episodes experienced while on prophylaxis. The pooled results revealed a difference favouring those on vitamin C when days confined to home and off work or school were taken as a measure of severity (p = 0.02), and when restricting to studies which used symptom severity scores (p = 0.16), and for the both measures of severity combined (p = 0.004). Seven trial comparisons that involved 3,294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C that was initiated after the onset of cold symptoms, and no significant difference from placebo was seen. Four trial comparisons that involved 2,753 respiratory episodes, contributed to the meta-analysis of cold severity during therapy and no significant difference from placebo was seen. In laboratory studies, differing methods of artificial transmission of virus to vitamin C or placebo treated volunteers in residential experiments gave different results. Volunteers infected by nasal installation showed small or no benefit from vitamin C, whereas a group who were infected more naturally, reported less severe symptom severity scores (p = 0.04).Reviewers' conclusionsThe 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. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapydid not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.This record should be cited as:Douglas RM, Hemila H, D'Souza R, Chalker EB, Treacy B. Vitamin C for preventing andtreating the common cold. The Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD000980.pub2. DOI: 10.1002/14651858.CD000980.pub2.BACKGROUNDNumerous animal studies with different species have shown that vitamin C affects resistance to diverse infections by viruses and bacteria (Hemilä 1997c) . It might therefore be expected that this vitamin would also play such a role in human beings, but its importance in this regardis unresolved. Since the early 1940s, a large number of controlled trials have been carried outto examine the possible effects of vitamin C on the common cold, a ubiquitous problem caused by a wide range of viral agents. The common cold causes enormous morbidity worldwide and the search for simple and effective preventive and/or therapeutic agents has been elusive. In 1970, the publication of Pauling 1970a, a book for the general public entitled "Vitamin C and the Common Cold" generated huge public interest which persists today. Linus Pauling was a double Nobel Laureate in chemistry and peace. In Pauling 1971a he carried out a meta-analysis in which he combined the p-values derived from four placebo-controlled trials 2by Fisher's method and found that there was strong evidence that vitamin C decreases the 'incidence of colds' (p = 0.003). In a second meta-analysis, Pauling 1971b focused on 'days ofillness per person' in the best of