Body mass index mediates the effect of the DASH diet on hypertension: Common metabolites underlying the association

Abstract

Background The Dietary Approaches to Stop Hypertension (DASH) diet is beneficial in reducing blood pressure; however, this may be a consequence of concurrent weight reduction. In the present study, we investigated whether body mass index (BMI) mediates the association between the DASH diet and hypertension and investigate common metabolic pathways. Methods We included 2424 females from the cross‐sectional TwinsUK cohort, with blood pressure, BMI and dietary intake measured within 1.01 (SD = 0.68) years and serum metabolomics profiling (591 metabolites). We constructed a mediation model to test the mediation effects of BMI on the total effect of the DASH diet on hypertension. To identify a metabolite panel associated with the DASH diet and BMI, we built random forest models for each trait, and selected the common metabolic contributors using five‐fold cross‐validation error. Results We found that BMI fully mediates the association between the DASH diet and hypertension, explaining 39.1% of the variance in hypertension. We then identified a panel of six common metabolites predicting both the DASH diet and BMI with opposing effects. Interestingly, at the univariate level, the metabolites were also associated with hypertension in the same direction as BMI. The strongest feature, 1‐nonadecanoyl‐GPC (19:0), was positively associated with the DASH diet (β [SE] = 0.65 [0.12]) and negatively with BMI (β [SE] = −1.34 [0.12]) and hypertension (odds ratio = 0.71, 95% confidence interval = 0.6–0.84). Conclusions We highlight the role of BMI in the mechanisms by which the DASH diet influences hypertension and also highlight common metabolic pathways. Further studies should investigate the underlying molecular mechanisms to increase our understanding of the beneficial ways of treating hypertension.

Gene–environment interactions in human health

“…This special issue of the Journal of Human Nutrition and Dietetics comprises a compilation of 12 original research articles that focus on associations between genes and environment as well as gene-environment interactions in human health, with a particular emphasis on diet, body composition and metabolic health. [1][2][3][4][5][6][7][8][9][10][11][12] Human gene-environment associations and interactions can be investigated using a range of study designs, including the classic twin study, which collects data from monozygotic and dizygotic twin pairs and typically uses some form of structural equation modelling to estimate the proportion of variation in a trait explained by genes, shared environment and unique environment. 13 Other study designs include the traditional candidate-gene study, which examines associations between genes and environmental exposures, usually where there is a known link between the gene and the exposure, or the more complex genome-wide association study, which usually assumes no prior hypothesis and examines the entire genome for interactions with various environmental exposures.…”

“…This brief editorial provides just a snapshot of some of the key insights into gene–environment interactions and relationships with health outcomes presented in the 12 original articles that follow 1–12 . The results and discussion presented herein highlight the important role of diet (and potentially other environmental factors) with respect to gene expression and ultimately an individual's health status.…”

“…Diet is one of the key aspects of the environment that impacts health along with others such as lifestyle, physical activity and the gut microbiome. This special issue of the Journal of Human Nutrition and Dietetics comprises a compilation of 12 original research articles that focus on associations between genes and environment as well as gene–environment interactions in human health, with a particular emphasis on diet, body composition and metabolic health 1–12 …”

“…Two articles in this special issue use data collected from twins to examine interactions between genes, diet, body composition and metabolic health 1,2 . Louca and colleagues took a case‐control approach with the TwinsUK data and reported that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was associated with lower risk of hypertension, but that the relationship is fully mediated by body composition (body mass index [BMI] in this case) 1 .…”

“…Two articles in this special issue use data collected from twins to examine interactions between genes, diet, body composition and metabolic health 1,2 . Louca and colleagues took a case‐control approach with the TwinsUK data and reported that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was associated with lower risk of hypertension, but that the relationship is fully mediated by body composition (body mass index [BMI] in this case) 1 . Uniquely, the analysis was extended to examine metabolites common to DASH adherence, BMI and hypertension, suggesting that relationships between diet and clinical health outcomes are underpinned by common metabolic pathways 1 .…”