Nontargeted Metabolite Profiling Discriminates Diet-Specific Biomarkers for Consumption of Whole Grains, Fatty Fish, and Bilberries in a Randomized Controlled Trial

Abstract

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.

Comparing metabolite profiles of habitual diet in serum and urine

“…Our findings for specific food-metabolite associations replicate $31 associations previously reported from clinical and population studies, including for fruit and juice (13)(14)(15)(48)(49)(50)(51)(52), red meat (13,(53)(54)(55), fish (15,51,56), nuts (15,51), liquor and wine (15,57), coffee (15,16,51,58,59), and multivitamin supplement (15) intake. Our serum findings parallel those reported by the Atherosclerosis Risk in Communities study (n = 1977) (51) and the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial (n = 502) (15) for metabolites associated with citrus (stachydrine, chiro-inositol, scyllo-inositol, and N-methyl proline), coffee (trigonelline, quinate, paraxanthine, 1-methylxanthine, and caffeine), fish (CMPF), nuts (tryptophan betaine), alcohol (ethyl glucuronide) and multivitamins (pyridoxate and pantothenate).…”

Identification and Quantitative Assessment of Uremic Solutes as Inhibitors of Renal Organic Anion Transporters, OAT1 and OAT3

“…69,70 It was reported that the fasting plasma hippuric acid and CMPF levels increased 3.3-and 2.6-fold in subjects on a Nordic diet. 71 Thus, levels of hippuric acid in subjects on a Nordic diet might be sufficiently high to inhibit OAT1 and OAT3. Interestingly, phenylacetic acid and benzoic acid are used to treat hyperammonemia in patients with urea cycle disorders under the brand name, Ammonul.…”

Application of Metabolomics to Assess Effects of Controlled Dietary Interventions

“…This phenomenon has been observed after diet rich in whole grain rye products versus refined cereal products in prostate cancer patients [23], after whole grain rye versus refined wheat diet in postmenopausal women with elevated serum total cholesterol concentrations [29], as well as by targeted analytical methods after 2-week intervention diet based on either whole grain-or refined grain-based foods [25]. Additionally, increase in several betaine compounds including pipecolic acid betaine, γ-butyrobetaine, and several unknown betaine signals after whole grain-rich diet was observed in the Healthgrain intervention, but not glycine betaine (generally termed in literature as betaine) [55]; therefore, complicated metabolism of betaine-related compounds may be involved in the health implications of whole grain products.…”

“…The study was carried out as a 12-week parallel-group intervention with 106 participants with features of metabolic syndrome who consumed either a healthy Nordic diet (whole-grain products, fatty fish, and bilberries), a whole-grain-enriched diet, or a control diet with refined-wheat breads and restrictions on fish and berries [55]. The non-targeted metabolite profiling by LCqTOF-MS showed marked differences in fasting plasma after the intervention diets compared with the control diet.…”