The prevalence of allergic diseases, particularly asthma, is on the increase. Asthma is a chronic disease with various etiologies and is expected to become more prevalent in the future. As a society develops, the prevalence and socioeconomic burden of asthma worsens. Approximately 339 million people worldwide have asthma, and in Korea, the prevalence of asthma continues to increase [1]. Factors responsible for the increase in the prevalence of asthma include increased air pollution caused by industrialization [2], changes in indoor living conditions, and exposure to allergens [3]. However, the factors that account for this trend remain unclear. Given that this trend occurs within a short period, attention should be paid to changes in environmental factors, such as dietary patterns.

One notable factor in dietary patterns is folic acid [4]. Folic acid, otherwise known as vitamin B9, is a water-soluble vitamin. It is involved in purine, pyrimidine, and amino acid synthesis, and is a source of methyl donors for DNA methylation [5]. Through gene-environment interactions, the pathogenesis of asthma causes epigenetic changes, including DNA methylation [6]. Folic acid plays a role in inflammatory reactions [7]. Low folic acid levels increase the risk of cardiovascular disease [8], inflammatory bowel disease, and rheumatoid arthritis [9]. However, the association between folic acid and allergic disease is uncertain.

Low folic acid levels are associated with increased risks of atopy and wheezing [4,10]. In Denmark, a low serum folate level is significantly associated with physician-diagnosed asthma [11]. However, other studies have reported no significant association between serum folic acid levels and physician-diagnosed asthma [4,12,13].

Folic acid and allergic diseases, including asthma, have been extensively reported, but available results are conflicting; thus, their association remains unclear. To our knowledge, research on folic acid levels and asthma among Asians with different dietary patterns from Westerners remains insufficient. Therefore, this study aimed to evaluate the relationship between serum folic acid levels and asthma in Koreans.

This study aimed to investigate the relationship between serum folic acid levels and asthma in the Korean population. We specifically examined people aged >10 years with no history of cancer affecting folic acid metabolism. Our multiple logistic regression analysis showed that the risk of asthma decreased as serum folic acid levels increased. We also observed the serum folic acid level in quintiles to assess the risk of asthma. Similarly, the asthma risk significantly increased when the serum folic acid level decreased. Therefore, serum folic acid levels were inversely associated with the risk of physician-diagnosed asthma.

Our findings are consistent with those of previous studies [11,14], which stated that serum folate levels were inversely correlated with the odds of asthma. In Denmark, a study involving 6,784 adult participants aged 30–60 years reported that folate deficiency was significantly associated with self-reported physician-diagnosed asthma (OR, 1.37; 95% CI, 1.05–1.79) [11]. In another cross-sectional study involving 8,083 children and adults aged 2–85 years in the US, serum folate levels were inversely associated with wheezing (OR, 0.6; 95% CI, 0.4–0.8) or atopy (OR, 0.7; 95% CI, 0.6–0.9), but no significant association with physician-diagnosed asthma was observed [4]. However, folate levels and asthma were not significantly associated in a case-controlled study in Egypt [12]. These differences in outcomes could be based on racial or sociological characteristics or caused by research errors; therefore, further research is required. In another Korean study, folic acid levels were not significantly different between groups with and without a history of acute asthma exacerbation in patients above the age of 65 years [15].

Some studies have reported an association between folic acid intake and asthma. A large case-control study of 1,030 UK adults found that the dietary intake of folic acid was inversely associated with physiciandiagnosed asthma (OR, 0.89; 95% CI, 0.89–0.98) [16]. In the 2019 KNHANES, the average daily folic acid intake was 80.7% of the recommended intake (men, 88.2%; women, 73.2%) [17]. Given that the association between folic acid and asthma is increasingly elucidated, folic acid intake needs to be improved.

This study had some limitations. First, the KNHANES has a crosssectional study design that makes it difficult to determine the direct causal relationship between folic acid levels and the pathophysiology and metabolism of asthma. Second, serum folic acid levels were collected once; therefore, they did not accurately reflect long-term folic acid conditions. Since it was not possible to confirm whether there was wheezing or asthma symptoms/attacks to evaluate current asthma symptoms, the study used a lifetime history of asthma, not the present. Therefore, it may be difficult to determine an exact association with the current state, which may require further investigation and research. Third, we did not examine the dietary folate intake of the participants. Fourth, comorbid conditions that could have affected folic acid were not excluded; moreover, the metabolism of folic acid is disrupted in patients with cancer [18]. Despite these limitations, the KNHANES is a strictly quality-managed program compared to other studies and data; hence, this study obtained an objective result. Furthermore, our study is a domestic study that used a large and representative sample of Koreans; thus, our research results can be generalized to all Koreans.

In conclusion, serum folic acid levels are inversely associated with asthma in Koreans above the age of 10 years. However, further research is needed to determine the cause-and-effect relationship between folate and asthma, and the potential role of folate supplementation in the primary prevention and treatment of allergic diseases.