title: Effect of dietary sodium restriction on human urinary metabolomic profiles.
abstract: OBJECTIVE
  Metabolomics is a relatively new field of "-omics" research, focusing on high-throughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary sodium restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR.
  
  
  METHODS
  Using stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 62±8 years) who had moderately elevated systolic BP (130-159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry-based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153±29 mmol/d) and low (70±29 mmol/d) sodium conditions, as well as their baseline (typical sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity).
  
  
  RESULTS
  Of the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a >40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation.
  
  
  CONCLUSIONS
  This proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and Division of Renal Diseases and Hypertension and Kristen.Nowak@ucdenver.edu.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Jablonski
authors.affiliation: Division of Renal Diseases and Hypertension and Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.affiliation: Division of Renal Diseases and Hypertension and.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
authors.forename: Candace J
authors.initials: CJ
authors.lastname: Bassett
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Racine
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure; D001916:Brachial Artery / Q000503:physiopathology; D003120:Colorado; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000178:diet therapy* / Q000503:physiopathology / Q000652:urine*; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D063177:Pulse Wave Analysis; D020127:Recovery of Function; D012039:Regional Blood Flow; D012694:Serine / Q000652:urine*; D013997:Time Factors; D016896:Treatment Outcome; D016482:Urinalysis; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D012694:Serine
keywords: endothelium; hypertension; metabolism; nutrition