Tea Is a Significant Dietary Source of Ellagitannins and Ellagic Acid.

The ellagitannin composition and the total content of ellagitannins in different types of tea were studied by high-performance liquid chromatography/ion-trap mass spectrometry. Strictinin and seven other isomers, tellimagrandin I, and ellagic acid were identified from tea infusions. The ellagitannin content in tea infusions was determined after acid hydrolysis and ranged from 0.15 to 4.46 mg of ellagic acid equivalent/g of tea in the infusions. The intake of ellagic acid after drinking a cup of tea brewed with 4 g of tea could range between 0.59 and 17.89 mg. These results indicate that tea can be a significant contributor to the dietary intake of ellagitannins. Urolithins, the gut microbiota metabolites produced in vivo from ellagic acid and ellagitannins, were detected in human urine after dietary tea beverage intake. Urolithin metabotypes A, B, and 0 were identified in volunteers after tea intake. These results suggest that the daily intake of ellagitannins from tea can have a role in tea health effects.

Pilot walnut intervention study of urolithin bioavailability in human volunteers.

A pilot intervention study was conducted in human volunteers (n = 4) to establish the bioavailability of urolithins, which are the terminal end-products of ellagitannin metabolism by the gastrointestinal microflora. Biospecimens (blood, feces, and urine) along with urolithins purified therefrom were analyzed for their antioxidant capacity in a range of in vitro assays. Urolithin metabolites were identified and quantitated in the biospecimens by negative ion mode HPLC-ESI-MS analysis. The data in this pilot study show that the metabolism of ellagitannins in the four volunteers gave rise to a diverse profile and a highly variable concentration of urolithins in urine. The concentration of glucuronidated urolithins in blood and urine did not correlate with antioxidant capacity. However, the antioxidant capacity of urine, but not plasma biospecimens, was highly correlated with uric acid concentration. The antioxidant capacity of fecal extracts correlated positively with the concentration of urolithin D in both the DPPH and FRAP assays, but not in the ORAC assay, which was entirely consistent with the in vitro assays for pure urolithin D.

Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients.

SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.

Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy.

The fate of anthocyanins, ellagic acid, and ellagitannins was studied following the consumption of 300 g of raspberries by healthy human volunteers and subjects with an ileostomy. Postingestion plasma and urine from the former and ileal fluid and urine from the latter group were collected and analyzed by HPLC-PDA-MS(2). Plasma from the healthy volunteers did not contain detectable quantities of either the native raspberry polyphenolics or their metabolites. The three main raspberry anthocyanins were excreted in urine in both healthy and ileostomy volunteers 0-7 h after ingestion, in quantities corresponding to <0.1% of intake. This indicates a low level of absorption in the small intestine. With ileostomy volunteers 40% of anthocyanins and 23% of the ellagitannin sanguiin H-6 were recovered in ileal fluid with the main excretion period being the first 4 h after raspberry consumption. The recovery of ellagic acid in ileal fluid was 241%, indicating hydrolysis of ellagitannins in the stomach and/or the small intestine. Urinary excretion of ellagic acid and an ellagic acid-O-glucuronide was <1% of intake. No intact or conjugated forms of ellagitannins were detected in urine from either healthy subjects or ileostomy volunteers. However, in healthy subjects, but not the ileostomists, ellagitannins were catabolized with the appearance of urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation.

Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects.

Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 +/- 0.05, 0.11 +/- 0.03, and 0.11 +/- 0.04 micromol . hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 +/- 0.42 hours) compared to PJ (0.65 +/- 0.23 hours) and POMxl (0.94 +/- 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl.