title: Nontargeted metabolite profiling discriminates diet-specific biomarkers for consumption of whole grains, fatty fish, and bilberries in a randomized controlled trial.
abstract: BACKGROUND
  Nontargeted metabolite profiling allows for concomitant examination of a wide range of metabolite species, elucidating the metabolic alterations caused by dietary interventions.
  
  
  OBJECTIVE
  The aim of the current study was to investigate the effects of dietary modifications on the basis of increasing consumption of whole grains, fatty fish, and bilberries on plasma metabolite profiles to identify applicable biomarkers for dietary intake and endogenous metabolism.
  
  
  METHODS
  Metabolite profiling analysis was performed on fasting plasma samples collected in a 12-wk parallel-group intervention with 106 participants with features of metabolic syndrome who were randomly assigned to 3 dietary interventions: 1) whole-grain products, fatty fish, and bilberries [healthy diet (HD)]; 2) a whole-grain-enriched diet with the same grain products as in the HD intervention but with no change in fish or berry consumption; and 3) refined-wheat breads and restrictions on fish and berries (control diet). In addition, correlation analyses were conducted with the food intake data to define the food items correlating with the biomarker candidates.
  
  
  RESULTS
  Nontargeted metabolite profiling showed marked differences in fasting plasma after the intervention diets compared with the control diet. In both intervention groups, a significant increase was observed in 2 signals identified as glucuronidated alk(en)-ylresorcinols [corrected P value (Pcorr) < 0.05], which correlated strongly with the intake of whole-grain products (r = 0.63, P < 0.001). In addition, the HD intervention increased the signals for furan fatty acids [3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF)], hippuric acid, and various lipid species incorporating polyunsaturated fatty acids (Pcorr < 0.05). In particular, plasma CMPF correlated strongly with the intake of fish (r = 0.47, P < 0.001) but not with intakes of any other foods.
  
  
  CONCLUSIONS
  Novel biomarkers of the intake of health-beneficial food items included in the Nordic diet were identified by the metabolite profiling of fasting plasma and confirmed by the correlation analyses with dietary records. The one with the most potential was CMPF, which was shown to be a highly specific biomarker for fatty fish intake. This trial was registered at clinicaltrials.gov as NCT00573781.
authors.affiliation: Institute of Public Health and Clinical Nutrition and kati.hanhineva@uef.fi.
authors.forename: Kati
authors.initials: K
authors.lastname: Hanhineva
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lankinen
authors.affiliation: Research Unit on Lipids and Atherosclerosis, Technological Center of Nutrition and Health, CIBERDEM, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, IISPV, Institut d'Investigació Sanitaria Pere Virgili, Reus, Spain; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Pedret
authors.affiliation: Institute of Public Health and Clinical Nutrition and Research Unit on Lipids and Atherosclerosis, Technological Center of Nutrition and Health, CIBERDEM, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, IISPV, Institut d'Investigació Sanitaria Pere Virgili, Reus, Spain; and.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schwab
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Marjukka
authors.initials: M
authors.lastname: Kolehmainen
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Mello
authors.affiliation: Research Unit on Lipids and Atherosclerosis, Technological Center of Nutrition and Health, CIBERDEM, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, IISPV, Institut d'Investigació Sanitaria Pere Virgili, Reus, Spain; and.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sola
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.affiliation: Institute of Public Health and Clinical Nutrition and VTT Technical Research Centre of Finland, Espoo, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Poutanen
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.affiliation: Institute of Public Health and Clinical Nutrition and.
authors.forename: Hannu
authors.initials: H
authors.lastname: Mykkänen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid; D004032:Diet; D002523:Edible Grain; D005215:Fasting; D005247:Feeding Behavior; D005260:Female; D005387:Finland; D005399:Fishes; D005527:Food, Fortified; D005638:Fruit; D005663:Furans / Q000097:blood; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D024821:Metabolic Syndrome / Q000097:blood; D055442:Metabolome; D011422:Propionates / Q000097:blood; D021241:Spectrometry, Mass, Electrospray Ionization; D029800:Vaccinium myrtillus
chemical_list: C468134:3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; D015415:Biomarkers; D005663:Furans; D011422:Propionates
keywords: CMPF; alkylresorcinol; dietary biomarker; hippuric acid; metabolomics; nontargeted metabolite profiling