Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years. To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms. We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012. We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials. Two review authors independently extracted data. We assessed 'incidence' of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean number of days of illness of cold episodes. Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64).Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration.Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials.The majority of included trials were randomised, double-blind trials. The exclusion of trials that were either not randomised or not double-blind had no effect on the conclusions. The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out. Nevertheless, given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them. Further therapeutic RCTs are warranted.

A number of controlled trials have previously found that in some contexts, vitamin C can have beneficial effects on blood pressure, infections, bronchoconstriction, atrial fibrillation, and acute kidney injury. However, the practical significance of these effects is not clear. The purpose of this meta-analysis was to evaluate whether vitamin C has an effect on the practical outcomes: length of stay in the intensive care unit (ICU) and duration of mechanical ventilation. We identified 18 relevant controlled trials with a total of 2004 patients, 13 of which investigated patients undergoing elective cardiac surgery. We carried out the meta-analysis using the inverse variance, fixed effect options, using the ratio of means scale. In 12 trials with 1766 patients, vitamin C reduced the length of ICU stay on average by 7.8% (95% CI: 4.2% to 11.2%; p = 0.00003). In six trials, orally administered vitamin C in doses of 1–3 g/day (weighted mean 2.0 g/day) reduced the length of ICU stay by 8.6% (p = 0.003). In three trials in which patients needed mechanical ventilation for over 24 hours, vitamin C shortened the duration of mechanical ventilation by 18.2% (95% CI 7.7% to 27%; p = 0.001). Given the insignificant cost of vitamin C, even an 8% reduction in ICU stay is worth exploring. The effects of vitamin C on ICU patients should be investigated in more detail.

Background: Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial). Methods: We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference lists of relevant publications. We included controlled trials in which the administration of vitamin C was the only difference between the study groups. We did not limit our search to randomized trials and did not require placebo control. We included all doses and all durations of vitamin C administration. One author extracted study characteristics and outcomes from the trial reports and entered the data in a spreadsheet. Both authors checked the data entered against the original reports. We used meta-regression to examine whether the vitamin C effect on ventilation time depends on the duration of ventilation in the control group. Results: We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1–6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001). Conclusions: We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group. The level of baseline illness severity should be considered in further research. Different doses should be compared directly in future trials.

Background: Randomized trials have shown that vitamin C shortens the duration of common colds. Some trials reported greater effects on severe cold symptoms compared with mild symptoms. This review systematically compares the effects of vitamin C on severe and mild common cold symptoms. Methods: We included all placebo-controlled trials of orally administered vitamin C in doses of at least 1 g/day for the common cold for people in good health at baseline. The analysis was restricted to trials which reported both the total duration of the common cold, and the severity of the common cold measured using severity scales, the duration of more severe stages of the cold, or proxies for severe colds such as days indoors. Findings were pooled using the inverse variance, fixed effect options of the metacont function of the R package meta to calculate the ratio of means estimate. Results: Fifteen comparisons from 10 trials which reported both mild and severe symptoms were identified. All trials were randomized and double-blind. Compared to placebo, vitamin C significantly decreased the severity of the common cold by 15% (95% CI 9–21%). The direct comparison of the effect of vitamin C on mild and severe symptoms was limited to five comparisons which found that vitamin C had a significant benefit on the duration of severe symptoms. In this subset, there was a significant difference in the size of the effect of vitamin C on the overall duration of colds versus the duration of severe colds (P = 0.002), and vitamin C had no significant effect on the duration of mild symptoms. Conclusions: The common cold is the leading cause of acute morbidity and a major cause of absenteeism from work and school. However, absenteeism is dependent on the severity of symptoms. The finding that vitamin C may have a greater effect on more severe measures of the common cold is therefore important. Further research on the therapeutic effects of vitamin C on the common cold should measure outcomes of differing levels of severity.

Hemilä H, et al. Infect Chemother. 2020 Jun;52(2):222-223. https://doi.org/10.3947/ic.2020.52.2.222

A previous meta-analysis found that high dose zinc acetate lozenges reduced the duration of common colds by 42%, whereas low zinc doses had no effect. Lozenges are dissolved in the pharyngeal region, thus there might be some difference in the effect of zinc lozenges on the duration of respiratory symptoms in the pharyngeal region compared with the nasal region. The objective of this study was to determine whether zinc acetate lozenges have different effects on the duration of common cold symptoms originating from different anatomical regions. We analyzed three randomized trials on zinc acetate lozenges for the common cold administering zinc in doses of 80–92 mg/day. All three trials reported the effect of zinc on seven respiratory symptoms, and three systemic symptoms. We pooled the effects of zinc lozenges for each symptom and calculated point estimates and 95% confidence intervals (95% CI). Zinc acetate lozenges shortened the duration of nasal discharge by 34% (95% CI: 17% to 51%), nasal congestion by 37% (15% to 58%), sneezing by 22% (−1% to 45%), scratchy throat by 33% (8% to 59%), sore throat by 18% (−10% to 46%), hoarseness by 43% (3% to 83%), and cough by 46% (28% to 64%). Zinc lozenges shortened the duration of muscle ache by 54% (18% to 89%), but there was no difference in the duration of headache and fever. The effect of zinc acetate lozenges on cold symptoms may be associated with the local availability of zinc from the lozenges, with the levels being highest in the pharyngeal region. However our findings indicate that the effects of zinc ions are not limited to the pharyngeal region. There is no indication that the effect of zinc lozenges on nasal symptoms is less than the effect on the symptoms of the pharyngeal region, which is more exposed to released zinc ions. Given that the adverse effects of zinc in the three trials were minor, zinc acetate lozenges releasing zinc ions at doses of about 80 mg/day may be a useful treatment for the common cold, started within 24 hours, for a time period of less than two weeks.