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Title: Serum untargeted metabolomic profile of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern

Author
item REBHOLZ, CASEY - Johns Hopkins University
item LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ZHENG, ZIHE - Johns Hopkins University
item APPEL, LAWRENCE - Johns Hopkins University
item CORESH, JOSEF - Johns Hopkins University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2018
Publication Date: 6/18/2018
Citation: Rebholz, C.M., Lichtenstein, A.H., Zheng, Z., Appel, L.J., Coresh, J. 2018. Serum untargeted metabolomic profile of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. American Journal of Clinical Nutrition. 108:1-13. https://doi.org/10.1093/ajcn/nqy099.
DOI: https://doi.org/10.1093/ajcn/nqy099

Interpretive Summary: The Dietary Approach to Stop Hypertension (DASH) dietary pattern is recommended for cardiovascular disease risk reduction. Assessing adherence to the DASH dietary pattern has been limited to subjective measures of intake and a few urinary biomarkers. The purpose of the study was to use metabolomics to identify serum compounds that are associated with adherence to the DASH dietary pattern. Untargeted metabolomic profiling was conducted in the serum collected at the end of three 8-week multi-center, randomized clinical feeding study; fruits and vegetables diet, fruits, vegetables and dairy products (DASH diet) or control diet. Serum levels of 44 known metabolites were significantly different among participants randomized to the DASH compared to both the control diet and fruits and vegetables diet. The ten most influential metabolites for discriminating between the DASH and control dietary patterns were: N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, beta-cryptoxanthin and 7-methylxanthine. In summary, an untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH diet and two other dietary patterns. These newly identified metabolites may be used as biomarkers of adherence to the DASH dietary pattern. This approach may be useful distinguishing among other dietary patterns in the future.

Technical Abstract: Background: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is recommended for cardiovascular disease risk reduction. Assessment of dietary intake has been limited to subjective measures and a few biomarkers from 24-h urine collections. Objective: The aim of the study was to use metabolomics to identify serum compounds that are associated with adherence to the DASH dietary pattern. Design: We conducted untargeted metabolomic profiling in serum specimens collected at the end of 8 wk following the DASH diet (n = 110), the fruit and vegetables diet (n = 111), or a control diet (n = 108) in a multicenter, randomized clinical feeding study (n = 329). Multivariable linear regression was used to determine the associations between the randomized diets and individual log-transformed metabolites after adjustment for age, sex, race, education, body mass index, and hypertension. Partial least-squares discriminant analysis (PLS-DA) was used to identify a panel of compounds that discriminated between the dietary patterns. The area under the curve (C statistic) was calculated as the cumulative ability to distinguish between dietary patterns. We accounted for multiple comparisons with the use of the Bonferroni method (0.05 of 818 metabolites = 6.11 x 10^-5). Results: Serum concentrations of 44 known metabolites differed significantly between participants randomly assigned to the DASH diet compared with both the control diet and the fruit and vegetables diet, which included an amino acid, 2 cofactors and vitamins (n = 2), and lipids (n = 41). With the use of PLS-DA, component 1 explained 29.4% of the variance and component 2 explained 12.6% of the variance. The 10 most influential metabolites for discriminating between the DASH and control dietary patterns were N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, beta-cryptoxanthin, and 7-methylxanthine (C statistic =0.986). Conclusions: An untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH diet and 2 other dietary patterns. This newly identified metabolite panel may be used to assess adherence to the DASH dietary pattern.