14 Dec Effect of Vitamin C on Exercise-induced Bronchoconstriction
Medical Research: What is the background for this study? What are the main findings?
Dr. Hemilä: I have a two decade interest in the effects of vitamin C on respiratory symptoms and I am the first author of the Cochrane review on vitamin C and the common cold. Since there is very strong evidence that vitamin C is better than placebo, in the Cochrane review we encourage common cold patients to try if vitamin C helps them.
In 2009, I was taking a look at the Cochrane review on vitamin C and asthma. I was puzzled with the text and figures since my own impression of the RCTs on vitamin C and asthma was quite different from what the review presented. Therefore I took a close look at the Cochrane review and I saw that it was sloppy. There were severe errors in data extraction and data analysis. For example, they used un-paired t-test when they should have used the paired t-test. That types of questions are very basic in biostatistics. I wrote a feedback to that Cochrane review and the review was withdrawn in 2013. It had been misleading readers for a decade. As a positive result of that incident, I became interested in the effects of vitamin C on asthma and I conducted a meta-analysis of three RCTs on vitamin C and exercise-induced bronchoconstriction (EIB). I calculated that vitamin C caused a 48% reduction (95% CI 33% to 64%) in the postexercise FEV1 decline. That study was published in BMJ Open in 2013 (http://www.ncbi.nlm.nih.gov/pubmed/23794586).
One of the three RCTs had also measured FEF60 which is an indicator of small airway obstruction and, in addition, that study reported pulmonary function tests at both 0 min and 5 min after exercise. In this new paper I analyzed that particular RCT in greater detail and showed that there was highly significant difference between the vitamin C and placebo days already at 0 min after exercise. I also found that at the 5 min time point vitamin C was beneficial for those patients who had lowest absolute post-exercise FEF60 levels, but there was no benefit for the rest. In this second paper, I reviewed the evidence indicating that vitamin C is involved in the metabolism of histamine, prostaglandins and cysteinyl leukotrienes, all of which appear to be mediators in the pathogenesis of EIB.
Medical Research: What should clinicians and patients take away from your report?
Dr. Hemilä: We need to consider safety, cost and the evidence of benefit. The confidence interval for the effect of vitamin C on post-exercise FEV1 is narrow and far from the null effect, which means that there is strong evidence of clinically meaningful benefit. Furthermore, vitamin C is inexpensive and safe. Two of the three RCTs on vitamin C and EIB gave vitamin C only as a single dose 1 to 2 hours before the exercise test. Thus, there is no indication that people would need to take vitamin C for a long time to benefit against stress caused by a session of exercise. In my view it is reasonable for a physically active person to test whether vitamin C is beneficial for him or her, if the person has documented EIB or suffers from respiratory symptoms such as cough or sore throat after taking vigorous exercise.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Hemilä: The authors of the 2009 version of the Cochrane review on vitamin C and asthma concluded that “Further methodologically strong and large-scale randomised controlled trials are needed in order to address the question of the effectiveness of vitamin C in asthma.” That kind of recommendation is not particularly imaginative. Moreover, when the effect is great, then large-scale RCTs are not needed. The three RCTs which I mention above had only 40 participants in all, yet the confidence interval for the effect of vitamin C was narrow and far from the null effect. Thus, we don’t need large-scale studies. Instead we need small and medium size studies, but they have to ask relevant questions, and they must be analyzed properly.
EIB is not a well-defined condition, instead the fall in FEV1 depends on the level of physical activity, and on the humidity and temperature of ambient air. Thus, future studies should cover different levels of such variables to see how the effect of vitamin C varies. Patients with mild and severe exercise-induced bronchoconstriction should both be included since that makes it possible to analyze the effects of vitamin C in relation to exercise-induced bronchoconstriction severity as I did in my analyses. In addition, the effect of supplementation probably depends on the level of dietary vitamin C intake which should also be controlled so that the effect of supplementation can be related to the dietary intake.
Citation: Review article: