Nontargeted metabolite profiling discriminates diet-specific biomarkers for consumption of whole grains, fatty fish, and bilberries in a randomized controlled trial

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.