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The developing story of antioxidants and asthma
  1. R Hubbard,
  2. A Fogarty
  1. Department of Respiratory Medicine, Nottingham City Hospital, Nottingham NG5 1PB, UK
  1. Correspondence to:
    Dr R Hubbard
    Department of Respiratory Medicine, Clinical Science Building, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK; richard.hubbardnottingham.ac.uk

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Antioxidant genotype may predict response to antioxidant supplements for asthma

The extent to which diet may have an impact on either the aetiology or the severity of asthma is a question that has generated much interest over the past decade.1,2 A number of observational studies have suggested that various dietary components—including higher levels of antioxidants,3,4 magnesium,5 and fish,6—have a protective influence on the risk of asthma. The implication of these findings is that, by changing our diet, we may be able to alter our risk of developing asthma or modify the severity of the disease, and these hypotheses have now been tested in a number of randomised controlled trials. Most intervention studies have included subjects with a diagnosis of asthma and hypothesised that nutrient manipulation may improve disease activity. To date there have been only a limited number of long term randomised controlled trials of dietary interventions in patients with asthma, with those using antioxidants such as vitamin C and vitamin E tending to suggest a benefit,7–9 while others using fish oil supplements have been disappointing.10 The study of dietary intervention for the prevention and treatment of asthma is still in its infancy and further clinical trials are required to enhance our understanding of the relationship between diet, the individual, and asthma.

Exposure to the pollutant ozone places an oxidative burden on the airways which, in turn, leads to airway inflammation and bronchoconstriction. In this issue of Thorax Romieu et al report on the use of this “model” of asthma to show in a clinical trial setting that dietary supplementation with the antioxidants vitamin C and E can ameliorate the deterioration in lung function that ozone exposure produces in children living in Mexico City.11 These results are consistent with existing data,8,12,13 and together these studies provide evidence that the adverse effects of an oxidative stress can be counteracted by dietary antioxidants, and that the beneficial effects of diet can be measured in terms of outcomes relevant to asthma. This model therefore provides a good opportunity to study the relationship between oxidative exposure, diet, host, and asthma outcome.

Romieu et al used data from their previous randomised controlled trial9 to show that host factors, particularly genotype, may have an important influence on the efficacy of dietary supplementation with vitamins C and E in preventing ozone provoked bronchoconstriction.11 The glutathione S-transferase supergene family is an important part of the cellular enzymic defence against endogenous and exogenous chemicals, and acts by conjugating the numerous byproducts of oxidative stress with glutathione.14 The full function of these enzymes is not understood, but those with the homozygous deletion polymorphism (GSTM1 null) are known to have diminished enzyme activity. Romieu et al hypothesised that, since the metabolic enzyme glutathione S-transferase (GSTM1) may help to protect against the adverse effects of ozone, children who have a homozygous deletion of the GSTM1 gene, and hence diminished endogenous antioxidant activity, may be particularly susceptible to the effects of ozone, and thus have the potential to benefit more from antioxidant supplementation. Their results showed that 39% of the trial participants, all of whom had asthma, had the null genotype and hence decreased enzyme activity. In children who received placebo there was an adverse impact of ozone on lung function, but this was restricted to children with the GSTM1 null genotype and no association was present in children with the active GSTM1 gene. In addition, the authors report that, in children with the GSTM1 null genotype who received placebo, the adverse effect of ozone was more marked in those with more severe asthma, although the criteria for defining asthma severity are not reported. Ozone did not reduce lung function in children who received antioxidant supplementation regardless of GSTM1 genotype. The authors conclude that GSTM1 has a role in protecting the airways against oxidative stress and that those children with diministed enzyme levels are more vulnerable to the effects of ozone. The importance of these findings is that, if replicated, they suggest that a sizeable proportion of the children in Mexico City are particularly vulnerable to the adverse effects of ozone, but that this increased risk can readily be counteracted by simple dietary supplementation methods. These data may be relevant to subjects in the UK since the 24 hour mean ozone concentrations reported in Mexico City are comparable to those recorded in Westminster, London during August 2003.15

The study by Romieu et al does have limitations which are acknowledged by the authors. The sample size was relatively small and not powered to allow formal tests of interaction between dietary supplementation, genotype, and outcome. In addition, data on the effect of genotype and dietary supplementation on symptoms are not reported. However, the findings suggest that, by identifying genes involved in relevant metabolic processes that are also related to asthma outcomes, we may be able to understand the importance of diet more clearly. This should lead to more appropriately designed epidemiological studies and interventional trials. The findings of Romieu et al are consistent with other studies which have shown that the adverse effect of in utero exposure to tobacco smoke on childhood wheezing illness is largely restricted to children of GSTM1 null genotype.16 Furthermore, polymorphisms at the locus of another member of the glutathione S-transferase supergene family (GSTP1) are associated with a sixfold lower risk of asthma.17 However, it is noteworthy that, in this latter study, no association was found between asthma and the GSTM1 genotype, in contrast to the findings of Romieu et al.

The understanding of how a “good diet” may help to reduce the prevalence and severity of asthma is still at an early stage, but the findings reported by Romieu et al are interesting and should stimulate more work in this field. As more antioxidant enzymes are genotyped and this knowledge is incorporated into both clinical trial and observational dietary datasets, we will understand better the interactions between diet, oxidative stress, and asthma. In the meantime it is tempting to speculate that all of us would be better off eating a healthy diet containing large amounts of fresh fruit and vegetables.

Acknowledgments

We thank Sarah Lewis for helpful comments on this editorial.

Antioxidant genotype may predict response to antioxidant supplements for asthma

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