Global associations of macronutrient supply and asthma disease burden

Abstract

We read with interest the work by Shin et al.,1 investigating the global disease burden of allergic disorders. They showed that the age-standardized prevalence of asthma has decreased over time on a global level. Following a similar theme, we curated asthma disease burden, macronutrient (protein, carbohydrate and fat) supply and gross domestic product (GDP) data around the globe (Supplementary Methods: Appendix S1). Our analysis found that in parallel to changes in asthma disease burden, GDP per capita2 has increased, and the global nutritional landscape has also changed, with increased supplies for all macronutrients, most noticeably for fat (Figure 1A,B). Both socioeconomic status and nutritional factors are emerging critical confounders for asthma.1 However, so far, most studies have neglected to consider their correlations and interactions, including among nutrients within diets (Figure 1C–E). They instead focused on individual parameters alone, like specific diets or foods.3 Here, we adopted a recently published approach2 to systematically interrogate the relationship between nutrient supply, a good proxy of food environment, socioeconomic status and asthma disease burden at a global scale over time. We focused on macronutrient supplies and their interactions, considering their important associations and implications for many facets of health.2 As generalized additive mixed models (GAMMs) can comprehensively analyse multiple parameters and their potential interactions, including their non-linear effects, this approach was used to analyse the effects on asthma disease burden of macronutrient supplies and GDP over time (Supplementary Methods: Appendix S1). In all analyses, a model considering the interactions of macronutrient supply and GDP, and an additive effect of time was favoured (Tables S1 and S3). This suggested interactive effects of macronutrients and socioeconomic status on asthma disease burden. The most recent year with all data available, 2018, is shown as a representative (Figure 1F,G, Figure S1, Tables S1 and S2). In brief, the predicted association between asthma prevalence and macronutrient supplies was visualized using response surfaces on macronutrient supply plots. We focused on the fat (x-axis) and carbohydrate (y-axis) supplies while holding protein at 25%, 50% and 75% quantiles of global supply. Across the response surfaces, red indicated higher asthma disease burden, while blue indicated lower. In our modelling, carbohydrate supply was most strongly associated with increases in asthma prevalence rates, while fat supply had the opposite effects (Figure 1F). This is illustrated by the purple isocaloric line, along which the total energy from macronutrients remained constant but fat is isocalorically substituted with carbohydrate. Increasing fat:carbohydrate ratio decreased the asthma prevalence. The effect of protein was less marked, evidenced by only a mild fluctuation of asthma prevalence across low, medium and high protein supplies. Similar patterns were found for asthma incidences (Figure 1G, Tables S3 and S4) independent of gender (Figures S2 and S3) and were not confounded by the total macronutrient energy supply. Along the red radial, changing total energy while holding the fat:carbohydrate ratio constant minimally impacted asthma disease burden. Notably, no difference was found between plant-based versus animal-based fat, while despite mild impact from total protein supply, extremely high or low animal-based protein supplies seemed to be associated with higher asthma burden (Figures S4 and S5). This represents the first study to link asthma to global food environments. Our results imply a driving role of carbohydrate supply for the asthma disease burden, after adjusting for the plausible interactions between macronutrients, total energy supply and socioeconomic status. Our analytical framework might also be instructive towards future estimation of asthma disease burden, guiding both medical research and public health policymaking. Interestingly, previous studies found that ketogenic diets, low in carbohydrates, might ameliorate established asthma,4 supporting our findings that ketogenic-like food environments are associated with lower asthma disease burden. Although further in-depth investigations are needed, as the macronutrient sources were not taken into account in the present study, diet quality might be an intriguing explanation for the positive association between carbohydrate supply and asthma. For example, high- and ultra-processed foods low in fibre have been found to be related to asthma development,3, 5 while we and others have previously shown that dietary fibre exhibited a strong immune regulatory influence, protecting against asthma.6, 7 Hence, future studies in more depth are warranted to investigate the associations between macronutrient supply and asthma, including other related socioeconomic and environmental factors like ancestry/ethnicity, physical activity, sleep and dietary patterns and qualities. Such studies will be critical for guidance to future clinical research and practice and public health interventions. Concept and design: Duan Ni, and Ralph Nanan. Acquisition, analysis and interpretation of data: Duan Ni, Alistair M. Senior, David Raubenheimer, Stephen J. Simpson, Laurence Macia, Ralph Nanan. Drafting of the manuscript: Duan Ni and Ralph Nanan. Critical revision of the manuscript for important intellectual content: All authors. This project is supported by the Norman Ernest Bequest Fund. The authors declare that they have no conflict of interest to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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