ORIGINAL ARTICLE AIRWAY DISEASES Atopy, asthma, and lung function in relation to folate and vitamin B 12 in adults B. H. Thuesen 1 , L. L. N. Husemoen 1 , L. Ovesen 2 , T. Jørgensen 1 , M. Fenger 3 , G. Gilderson 4 & A. Linneberg 1 1 Research Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark, Glostrup, Denmark; 2 Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark; 3 Department of Clinical Biochemistry and Molecular Biology, Hvidovre Hospital, Hvidovre, Denmark; 4 Siemens Healthcare Diagnostics, Go ¨ teborg, Sweden To cite this article: Thuesen BH, Husemoen LLN, Ovesen L, Jørgensen T, Fenger M, Gilderson G, Linneberg A. Atopy, asthma, and lung function in relation to folate and vitamin B 12 in adults. Allergy 2010; 65: 1446–1454. The epidemics of allergy and asthma have consistently been linked to a Westernized, affluent, and urban lifestyle (1). In recent years, the impact of nutrition on asthma and atopy has received great attention (2), and it has been hypothesized that changes in dietary intake of micronutrients may be important factors. Countries without food fortification with folic acid, includ- ing Denmark, usually demonstrate insufficient intakes and low status of folate (3). Folate deficiency is known to alter the cell-mediated immune response (4) by reducing the proportion of circulating CD8+ T cells and thereby increasing susceptibility to infections (5). In addition, folate deficiency has been suggested to be associated with the development of atopy – for example, by inhibition of the remethylation cycle causing an altered TH1/TH2 balance (6). On the other hand, a folate-enriched diet has been shown to increase allergic responses and lung inflammation in mice, suggesting that high levels of folate, which serves as a source of methyl donors for DNA methylation, induce epigenetic changes promoting allergic diseases (7). Vitamin B 12 (cobala- min) (B 12 ) and folate are both required as cofactors in the metabolic process of remethylating homocysteine to methionine (8) and thereby the two B-vitamins interact in a number of biological processes. The common polymorphism of the methylene-tetrahydro- folate reductase (MTHFR) gene (C677T) is a functional poly- morphism leading to reduced enzymatic activity and altered folate metabolism (9). The MTHFR-C677T polymorphism is Keywords asthma; atopy; folate; lung function; vitamin B 12 . Correspondence Betina H. Thuesen, Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark. Tel.: +45 43233274 Fax: +45 43233977 E-mail: beheth01@glo.regionh.dk Accepted for publication 10 March 2010 DOI:10.1111/j.1398-9995.2010.02378.x Edited by: Thomas Bieber Abstract Background: Recent studies suggested low serum folate and impaired folate metabo- lism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B 12 (B 12 ) deficiency with different phenotypes of asthma and atopy. Methods: A random sample of 6784 persons from a general population aged 30– 60 years participated in a health examination in 1999–2001, and 4516 (66.6%) of those also participated in a follow-up examination 5 years later. The examinations included spirometry, measurements of serum folate and B 12 , specific IgE to inhalant allergens, total IgE, and genotyping of the MTHFR-C677T polymorphism – a genetic marker of impaired folate metabolism. Information about dietary intake of folate and B 12 , asthma diagnosis, and airway symptoms was obtained by question- naires. Results: Low serum folate levels and the TT genotype of the MTHFR-C677T poly- morphism were associated with increased prevalence of self-reported doctor-diag- nosed asthma [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05–1.79 and OR 1.52; 95% CI 1.12–2.06, respectively] and attacks of shortness of breath (OR 1.43, 95% CI 1.14–1.79 and OR 1.47; 95% CI: 1.14–1.91, respectively). We found no significant associations with lung function or atopic outcomes. Serum levels of B 12 and dietary intake of folate and B 12 were not associated with asthma or atopy. Conclusions: We found that two objective markers of folate deficiency were associ- ated with self-reported doctor-diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy. Allergy 1446 Allergy 65 (2010) 1446–1454 ª 2010 John Wiley & Sons A/S