Multivitamin consumption and childhood asthma: a cross-sectional study of the NHANES database

Asthma is one of the most common chronic diseases of childhood, and the disease burden is in a rising trend globally [1, 2]. The mean worldwide prevalence of asthma in 2020 was about 13% in adolescents and 11% in children [3]. Although inhaled corticosteroids are the most effective and commonly used treatment for persistent asthma [4], some of the children may suffer from frequent and severe asthma attacks, causing deterioration of lung function [5], and thus increasing the psychological burden on both children and parents [6].

Diet is a common modifiable factor related to the airway inflammation and asthma [7]. High dietary inflammatory index has been reported to be associated with high-burden of childhood asthma [8]. Vitamins are obtained from the daily diet and play important roles in maintaining normal physiological functions of the human body, and take part in the occurrence and development of a variety of diseases [9]. Anti-oxidative vitamins, such as vitamin C (VC) and vitamin E (VE), have anti-inflammation effects and are involved in the oxidative stress caused by scavenging reactive oxygen species (ROS), and thus may reduce the risk of asthma [10, 11]. On the other hand, dietary intake of a number of vitamins may be associated with an increased risk of asthma. A Lasso regression analysis conducted by Qu et al. [12] found that dietary vitamin B12 (VB12) consumption was positively associated with childhood asthma. Vitamins including folic acid, VB12, and choline are the common methyl donors of human DNA methylation, which may promote the risk of allergic airway diseases [13, 14]. However, existing researches have mainly explored the association between a single vitamin intake and childhood asthma, which not take multivitamins into consideration.

Actually, human beings are exposed to multiple dietary vitamins, and there may be potential synergistic or antagonistic effects between different vitamins on diseases’ progression. Herein, the current study aims to explore the overall effect of dietary consumption of multivitamins on childhood asthma, and hope our findings could provide some information on diet management in children and adolescents who are at high-risk of asthma.

This study explored the association between multivitamins and childhood asthma. We found that elevated dietary multivitamins consumption was overall associated with decreased odds of childhood asthma. To be specific, for each 1-unit increase in VK consumption, the odds of childhood asthma decreased. Among the multivitamins, VD and VB2 had positive associations with childhood asthma, whereas that VC had a negative one. Moreover, no potential interaction between every two vitamins of the multivitamins on the childhood asthma was found.

To the best of our knowledge, no study has explored the relationship between multivitamins intake and asthma in children and adolescents. A Swedish birth cohort study on using of multivitamin supplements in relation to allergic disease in 8 years old children found no relationship between current use of multivitamins and the risk of allergic disease [25]. However, Milner et al. [26] showed that early vitamin supplementation was linked to an increased risk for asthma in Black children. Another study investigated the association between multivitamin supplements intake and asthma development in Norwegian adults, which also demonstrated that regular multivitamin supplements was related to an increased OR for incident asthma [27]. Similarly, in the current study, we found an overall negative effect of dietary multivitamins intake on the odds of asthma in children and adolescents. Childhood asthma is an allergenic disease that influenced by both genetic and environmental factors [28]. Comparing with previous studies, participants in our research had different age, race, and multivitamins intake pattern, which may all affect the influencing factors related to childhood asthma. The average age of Children with asthma in our study was 10 years old, and 1,065 (13.0%) of them were Black. Aging directly and significantly leads to future exacerbations in asthma [29]. A study has reported that Black and Latinx Americans had a higher prevalence and greater morbidity of asthma than the White Americans [30]. Racial/racial inequities such as socioeconomic status, environmental exposures, and health care access/quality are social determinants of health, which result in excess burden of asthma prevalence/incidence [30, 31]. Herein, we have adjusted these covariates and also found an approximately negative relationship between multivitamins consumption and childhood asthma, which relatively made our results more robust.

Among the multivitamins, we compared the PIP of the effect of each vitamin on asthma, and the results showed that VC, VD, and VB2 were the mainly contributors. Also, when all the vitamins were fixed to the median, dietary VD and VB2 intakes were positively associated with the odds of childhood asthma, while that VK had a negatively relationship. The role of VC as an antioxidant vitamin in allergic diseases such as asthma has been extensively studied [32, 33]. A systematic review and meta-analysis of randomized controlled trials by Kumar et al. [34] suggested that VD supplementation might not have any protective effect in childhood asthma. Gale et al. [35] found that exposure to maternal concentrations of 25(OH)-VD >75 nmol/L compared to those <30 nmol/L in late pregnancy had an increased risk of offspring asthma at 9 years old. However, some other studies showed opposite results that higher VD concentration may reduce the risk of developing childhood asthma [36, 37]. In the pathogenesis of childhood asthma, Lung helper T cell 2 (Th2) causes airway hyper-responsiveness and remodeling through inflammatory pathways [38]. Supplement with VD and VC increases in the production of pro-inflammatory cytokines, and can reduce respiratory infections, which suggested they can enhance the immune response, thereby reducing the risk of asthma [10, 39]. However, further studies are needed to make these causal relationships clearer. VB2, namely riboflavin, is the vitamin that most frequently induces allergic reactions [40]. VB2 directly affects both vasodilatation and bronchoconstriction in conjunction with the triggering of mast cell degranulation [41]. High level of VB2 may result in the bronchial hyperresponsiveness and contribute to the development of childhood asthma. On the contrary, we found an opposite relationship between VK intake and the odds of asthma. In fact, menaquinone (vitamin K2) was used as an effective bronchial asthma drug [42]. Shibata et al. [43] found that the VK-dependent soluble protein known as growth arrest-specific protein (Gas) 6 levels exerted in allergic airway disease. According to our results, although it is statistically significant, the estimated association of asthma with VK consumption was very small (OR=0.99), indicating that children and adolescents with high-risk of asthma need to focus on the regular examination on VK concentration, and timely supplement appropriate dietary VK under medical supervision in clinical practice, which may further be beneficial to prevention of childhood asthma. However, the opportune prevention dosage as well as the specific mechanism of the potential protective effect of VK on childhood asthma is still needed further exploration.

Through the BKMR model, we also investigated the interactions between every two vitamins among the multivitamins on childhood asthma. When fixed one of the two vitamins at the 10th, 50th, and 90th percentiles respectively (with the rest ten vitamins at the median), no potential interactions between these two vitamins on childhood asthma was found. Several studies have reported potential interactions of different vitamins and the underlying mechanisms in different physiological process. The B-group vitamins including B2, B6, folic acid, betaine, choline, and B12 are reported play roles in human DNA methylation [44]. Folic acid, VB12, and choline are a source of methyl donors for DNA methylation, and have been extensively studied in asthma [45]. Besides, the BKMR is a recent developed approach for estimating the health effects of multi-pollutant mixtures, and is of increasing interest in environmental epidemiology [46]. In addition to multi-pollutant mixtures, BKMR has also been used in studying the exposure to some conventional trace elements. Predictive process method of BKMR leads to a substantial reduction in the runtime, without a major decrease in accuracy, and in the setting of a larger number of exposures and a dichotomous outcome, so that the probit BKMR implementation is able to correctly identify the variables included in the exposure-response function [46].

There are strengths and limitations in this study. Our study sample size was large and representative due to the data was extracted from the NHANES database. We used the BKMR model to explore the overall effect of multivitamins consumption on childhood asthma, which may provide some references for the assessment and guidance of dietary multivitamins supplement in children and adolescents with high-risk of asthma. Some limitations of this study must be considered when interpreting the results. This is a cross-sectional study that could not clarify the causal relationship between multivitamins intake and childhood asthma. Data of vitamins intake were collected by 24-hour dietary recall, which may cause recalling bias. Besides, the 24-hour dietary recall only reflected recent dietary trends, but the long-term dietary status was unavailable. The diagnosis of asthma was self-reported, which perhaps may underestimate the actual prevalence of childhood asthma. Moreover, due to the limitation of database, the impact of under-reporting of those with missing data cannot be ignored.

Dietary consumption of multivitamins was overall negatively associated with the odds of childhood asthma. Our findings recommended that children and adolescents should increase the intake of VC-rich foods, whereas control the dietary consumption of VD and VB2 in daily life.