Novel Urinary Biomarkers of Orange Juice Consumption, Interindividual Variability, and Differences with Processing Methods

Abstract

Untargeted metabolomics identified urinary biomarkers able to discriminate between the intake of fresh hand-squeezed and industrially processed orange juices. Processing led to an upregulation in the excretion of hydroxy-polymethoxyflavone sulfates, abscisic acid, and sinapic acid 4′-glucuronide. The demethylated polymethoxyflavone metabolites were produced with a significant interindividual variability suggesting that they could originate from gut microbiota metabolism. No correlation between the excretion levels of flavanone and polymethoxyflavone metabolites was observed, showing that gut microbiota metabolism differences could be behind the interindividual variability. Subjects with a high excretion level of hesperetin conjugates could be low or high polymethoxyflavone excretors. Flavanone phase II metabolites were primarily glucuronides, while those of demethylated polymethoxyflavones were mainly sulfates. A comparative study with the available demethylated polymethoxyflavone standards suggested that the metabolites produced in humans could be tentatively 4′-hydroxy- and/or 3′-hydroxy-polymethoxyflavone sulfates. This study is the first to describe the bioavailability and metabolism of citrus juice polymethoxyflavones in humans.

Health associations of liver enzymes and inflammatory scores with urinary citrus flavonoid metabolites

“…Tomás-Navarro et al found that the main flavanones detected in urine were phase II conjugated derivatives of naringenin and hesperetin after ingesting 400 ml of citrus fruit (orange and mandarin). 23 Previous studies from the European Prospective Investigation into Cancer (EPIC) 53,58 and PREDIMED-Plus showed that flavonoids were the main contributors to total (poly)phenol intake in the Spanish population. 54,55 On average, the consumption of citrus fruit was 151 g per day (around 35% of the total mean fruit intake) in our population.…”

“…13 Third, the flavonoid metabolites evaluated in this study were limited and therefore influence our conclusions, but the flavanone metabolites used in the present study are well correlated with citrus fruit intake, and they have been suggested as biomarkers of citrus consumption. 23,55,57…”

“…They are mainly excreted in urine as phase II conjugates that are recognized as biomarkers of citrus-derived food consumption. 23…”

“…22 In this context, the use of dietary biomarkers for assessing directly the dietary intake/status could avoid the bias of the dietary self-reported data. 22,23 Experimental and human studies have evidenced that flavonoids might exert hepatoprotective properties, 24 cardiovascular benefits, 18,25,26 anti-metastatic activity, and improvement in the metabolic profile. 19 Flavonoids are widely present in many plant-based foods, such as berry fruits, red wine, citrus fruits, grapes, apples, tea, soybeans, and others.…”

Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid

“…After the last intake, a urine sample was collected and immediately stored at −20 °C, until analysis . Institutional ethical approvals were unnecessary as the experiments were carried out with freely available foodstuff, and only urine samples were collected, as advised by the Ethical Committee for previous studies . The volunteers gave written informed consent.…”