Vitamins linked to asthma risk?

“A low intake of vitamins A and C could raise the risk of asthma,” BBC online has said. The news service reports research by Nottingham University that pooled results from a number of studies on vitamin intake and asthma risk. The study concluded that low levels of vitamin C increased asthma risk by 12%. The link with vitamin A (found in cheese, eggs and fish) was also significant but could not be measured. The lead researcher said that larger scale studies are now important to see if there is a causal link between vitamin intake and asthma.

This systematic review analysed data from 40 observational studies, in which researchers collected data from other studies rather than conducting experiments themselves.  While this review was well conducted, its results are subject to the limitations and biases in the original research it combined. Also, the observational studies analysed cannot establish causation for a condition such as asthma, as they are only able to find how common a particular factor is among affected people. Given the weaknesses in the original studies, the most reasonable message is a call for further research, particularly for randomised trials of vitamin supplements.

Where did the story come from?

Drs S Allen, JR Britton and JA Leonardi-Bee from the University of Nottingham carried out this study. The University of Nottingham also funded the study that was published in the peer-reviewed medical journal Thorax.

What kind of scientific study was this?

This study was a systematic review of several previous studies that had investigated the association between vitamins A, C and E and asthma.

There is an apparent inconsistency within the research in this area, with observational studies finding that vitamins reduce asthma risk, while randomised trials have not generated consistent findings. This new systematic review was of observational studies (case control, cross sectional and cohort studies), and aimed to derive a pooled estimate of the association between vitamins and asthma risk.

The researchers searched five databases of clinical studies for any that might be relevant. The researchers assessed these studies for relevance and quality, and then extracted the results from each and combined them using meta-analysis. From this, they got a single result that measured the size of the link between vitamin levels and risk of asthma. They were specifically interested in the effects of vitamin A, vitamin C and vitamin E on asthma, asthma and wheeze, and wheeze and airway reactivity.

What were the results of the study?

The researchers found and assessed 2624 studies in their search. Of these, they included 40 studies in their systematic review. They assessed several different outcomes and separately analysed dietary intake and serum levels of each vitamin. Some studies had assessed the odds of asthma in relation to particular vitamin levels while others reported serum levels of the vitamin in different asthma groups. We report a selection of the study results here.

In total, 21 studies assessed the link between vitamin A (or its derivatives) and asthma or outcomes of wheezing symptoms. Pooling three case control studies suggested that the average self-reported dietary intake of vitamin A was significantly less in people with asthma, although there was no statistically significant link found between serum levels of vitamin A and asthma.

When assessing outcomes by asthma severity, pooling two case-control studies found those with severe asthma had lower dietary intakes of vitamin A. In addition, three studies which relied on physicians to diagnosed cases of severe asthma found lower serum levels of vitamin A in people with severe disease compared to those with milder disease. This link was not apparent when the studies where severity was reported by the patients or childrens parents..There was no link between dietary intake of vitamin A and wheeze but those with lower serum levels seemed to have a reduced risk of wheezing.

The researchers combined nine studies looking at the effect of dietary vitamin C and asthma wheeze, and found that low levels were linked with a 12% higher risk of asthma. For the serum vitamin C levels, studies were too different from each other (heterogeneous) to derive a pooled estimate.

There was no difference in the average dietary intake of vitamin C between those with and without asthma. Increased risk of wheeze was associated with lower vitamin C intake.

What interpretations did the researchers draw from these results?

This systematic review and meta-analysis showed a consistent negative association between intake of antioxidant vitamins and asthma status, although the findings in relation to wheeze symptoms were less consistent.

There is a discrepancy between this observational data and the findings of randomised controlled trials (RCTs): a recent Cochrane review of RCTs looking at the effects of dietary vitamin C has, concluded that there is no appreciable effect. The researchers discuss three possible reasons for this discrepancy, including the fact that observational data may be flawed and subject to bias.

Alternatively, an explanation could be that the link between vitamins and asthma is not a causal one, rather one linked to other dietary or non-diet factors. Another possibility for the conflicting results is that dietary factors in early life are important, but this is yet to be tested in randomised trials.

What does the NHS Knowledge Service make of this study?

The researchers highlight the weaknesses associated with this study:

• They included studies that used different methods to determine the level of antioxidants used. They also acknowledge that the majority of the studies they included were not designed to establish causal links between food intake and asthma, i.e. they assessed the levels of antioxidant vitamins after the onset of asthma.
•  The biases in this meta-analysis are similar to the biases of the underlying studies, the majority of which did not control for confounders such as age, socioeconomic status, smoking and BMI. These factors could be contributing to the association seen between vitamin intake and asthma or wheeze outcomes.

There are a number of reasons – highlighted by the researchers – why the epidemiological evidence for the association between vitamin intake and asthma and wheeze risk is weak. There are therefore many caveats associated with interpreting the evidence from the available observational studies.

Importantly, the observational evidence on vitamin C varies from the experimental evidence from randomised trials, which was assessed in the recent Cochrane review. This systematic review looked at 330 participants across nine studies, finding no appreciable effect of vitamin C supplementation on asthma risk. Given these inconsistencies, the most important conclusions in this paper are that observational studies are useful for identifying an association, as they have done here, but that they cannot establish causation. The researchers say that it is “now important to carry out larger-scale studies to clarify the link and to see if there is a direct cause between vitamin intake and asthma”.