Review and feature article
Diet as a risk factor for atopy and asthma

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It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified.

Section snippets

The antioxidant and lipid hypotheses

In 1994, we argued that the increases in asthma and atopic diseases were unlikely to be a consequence of the air we breathe becoming increasingly toxic.4 There had been well-documented decreases in atmospheric pollution and cigarette smoking, and there was little evidence for increased exposure to aeroallergens. Instead, we hypothesized that the increase in asthma and atopy had resulted from increasing population susceptibility. We noted that the increase in asthma and atopy had been preceded

Vitamin C

Water-soluble vitamin C provides intracellular and extracellular aqueous-phase antioxidant capacity primarily by scavenging oxygen free radicals and suppressing macrophage secretion of superoxide anions. In general, most studies of dietary vitamin C have reported beneficial associations with ventilatory function, a smaller number have reported associations with asthma, and very few, if any, have shown associations with atopic disease.

Many epidemiologic studies have demonstrated that dietary

Antioxidant intervention studies

The epidemiologic studies discussed above suggest that there are beneficial associations between asthma and atopic disease and dietary antioxidants, such as vitamin C, vitamin E, some carotenoids, selenium, and antioxidant-rich fruits. There have been many intervention studies, the majority of which have supplemented with vitamin C. Studies of vitamin E and selenium supplementation are few in number. In general, the results of these supplementation studies have been disappointing, with many

Antioxidants, asthma, and atopic disease: Possible mechanisms

The respiratory airways are particularly vulnerable to oxidative damage, and to counteract this, numerous enzymatic and nonenzymatic antioxidant defense mechanisms are present.34 In experimental models oxidants induce many features of asthma by inducing release of proinflammatory mediators, including cytokines, chemokines, and eicosanoid metabolites.35 Oxidant stress also activates gene expression of 2 pivotal inflammatory regulators, nuclear factor κB and activator protein 1.35

There is an

Observational studies of lipids

Several cross-sectional studies have reported beneficial associations between dietary fish intake, asthma, and atopic disease.51, 52 Hodge et al51 reported that in children aged 8 to 11 years the risk of current asthma was significantly reduced in those who included fresh oily fish in their diet. A number of studies of adult populations have reported no association between dietary fish intake and asthma, respiratory symptoms, and ventilatory function,53 and Takemura et al54 reported an adverse

Lipid intervention studies

As outlined above, investigation of asthma and dietary lipids has pursued the suggestion that asthma and atopy are a consequence of increasing n-6 PUFA intake and decreasing n-3 PUFA consumption and effects on inflammatory mediators and TH cell differentiation. Studies of atopic dermatitis have focused on reduced activity of Δ6-desaturase enzyme and consequent effects on epidermal structure-function and TH cell differentiation. This is probably why there has been an emphasis on increasing

Conclusion

Epidemiologic studies have reported associations between dietary antioxidant and lipid intakes and asthma and atopic disease. With the possible exception of n-6 PUFA supplementation for atopic dermatitis, a major criticism of the dietary hypotheses is the generally disappointing results of intervention studies. However, the realization that dietary habits are established early in life and that fetal and early life factors influence the development of asthma and atopic disease has moved the

References (78)

  • M.P. Nair et al.

    The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL-4) cytokine gene expression by normal peripheral blood mononuclear cells

    Biochim Biophys Acta

    (2002)
  • C.S. Broome et al.

    An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status

    Am J Clin Nutr

    (2004)
  • D.W. Jeong et al.

    Protection of mice from allergen induced asthma by selenite

    J Biol Chem

    (2002)
  • Y. Takemura et al.

    The relationship between fish intake and the prevalence of asthma: the Tokorozawa Childhood asthma and Pollinosis Study

    Prev Med

    (2002)
  • D.F. Horrobin

    Essential fatty acid metabolism and its modification in atopic eczema

    Am J Clin Nutr

    (2000)
  • M.S. Manku et al.

    Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy

    Prostaglandins Leukot Med

    (1982)
  • K. Wakai et al.

    Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross sectional study in Japan

    Ann Epidemiol

    (2001)
  • K.S. Broughton et al.

    Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production

    Am J Clin Nutr

    (1997)
  • J. Berth-Jones et al.

    Placebo controlled trial of essential fatty acid supplementation in atopic dermatitis

    Lancet

    (1993)
  • J.K. Peat et al.

    Three year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study

    J Allergy Clin Immunol

    (2004)
  • C.J.A.W. Van Gool et al.

    γ-Linolenic acid supplementation for prophylaxis of atopic dermatitis—a randomized controlled trial in infants at high familial risk

    Am J Clin Nutr

    (2003)
  • J.A. Dunstan et al.

    Fish oil supplementation in pregnancy modifies neonatal allergen specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial

    J Allergy Clin Immunol

    (2003)
  • P. Burney

    Epidemiological trends

  • A. Devenny et al.

    Respiratory symptoms and atopy in children in Aberdeen: questionnaire studies of a defined school population repeated over 35 years

    BMJ

    (2004)
  • A. Seaton et al.

    Increase in asthma: a more toxic environment or a more susceptible population?

    Thorax

    (1994)
  • Department for Environment, Food and Rural Affairs, HMSO. Consumption of selected household foods (GB) 1942 to 2000....
  • A. Seaton et al.

    The increase in hay fever: pollen, particulate matter and SO2 in ambient air

    QJM

    (1996)
  • P.N. Black et al.

    Dietary fat and asthma: is there a connection?

    Eur Respir J

    (1997)
  • T. Obata et al.

    Eicosapentaeanoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells

    Clin Exp Allergy

    (1999)
  • P.C. Calder et al.

    Fatty acids and lymphocyte functions

    Br J Nutr

    (2002)
  • F.D. Gilliland et al.

    Children's lung function and antioxidant vitamin, fruit, juice and vegetable intake

    Am J Epidemiol

    (2003)
  • G. Hu et al.

    Antioxidants and pulmonary function: the third National Health and Nutrition Examination Survey (NHANES III)

    Am J Epidemiol

    (2000)
  • J.R. Britton et al.

    Dietary antioxidant vitamin intake and lung function in the general population

    Am J Respir Crit Care Med

    (1995)
  • R.N. Rubin et al.

    Relationship of serum antioxidants to asthma prevalence in youth

    Am J Respir Crit Care Med

    (2004)
  • R.I. Harik-Khan et al.

    Serum vitamin levels and the risk of asthma in children

    Am J Epidemiol

    (2004)
  • C. Bodner et al.

    Antioxidant intake and adult-onset wheeze: a case-control study

    Eur Respir J

    (1999)
  • A. Soutar et al.

    Bronchial reactivity and dietary antioxidants

    Thorax

    (1997)
  • H.J. Schünemann et al.

    The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population

    Am J Respir Crit Care Med

    (2001)
  • B.K. Butland et al.

    Diet, lung function and lung function decline in a cohort of 2512 middle aged men

    Thorax

    (2000)
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