Absorption and Metabolism of Dietary Phenolics From Raspberries

Dietary Modifications Clinical Trial

Official title:

Bioavailability of Anthocyanins in Humans Following the Ingestion of Berries and Grapes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02520596
• Other study ID #: DDR-002
• Status: Completed
• Phase: N/A
• First received: July 31, 2015
• Last updated: August 7, 2015
• Start date: November 2013
• Est. completion date: June 2014

Study information

• Verified date: August 2015
• Source: University of Parma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

Red raspberries are a rich source of (poly)phenolic compounds, the main components being anthocyanins and ellagitannins. There is growing evidence linking consumption of these compounds with beneficial effects on human health. However, the mechanisms involved remain poorly understood principally because of a limited understanding of the bioavailability of ellagitannins and anthocyanins. This study aims to explore the identity and amounts of the phenolic metabolites of anthocyanins and ellagitannins in human plasma and urine following acute ingestion of raspberries. For this purpose ten healthy volunteers were feed 300 g of blended raspberries containing in total 293 μmol anthocyanins and 250 μmol ellagitannins. All urine excreted over 48 h after the ingestion of raspberries was collected and blood samples were collected before (0 h) and after raspberry consumption up to 24 h. Metabolites were identified and quantified by ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• in general good health

Exclusion Criteria:

• smoking

• pregnancy

• vegetarian

• sustained use of nutritional supplements

Study Design

Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dietary Modifications

Intervention

Other:
• Bioavailability of Raspberry polyphenols

Locations

Country	Name	City	State
Italy	University of Parma - Department of Food Science	Parma

Sponsors (3)

Lead Sponsor	Collaborator
University of Parma	National Processed Raspberry Council, University of Glasgow

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation. 2013 Jan 15;127(2):188-96. doi: 10.1161/CIRCULATIONAHA.112.122408. — View Citation

Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. Am J Clin Nutr. 2013 May;97(5):995-1003. doi: 10.3945/ajcn.112.049247. — View Citation

de Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD. The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol. 2014 Jul;171(13):3268-82. doi: 10.1111/bph.12676. — View Citation

Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013 May 10;18(14):1818-92. doi: 10.1089/ars.2012.4581. Epub 2012 Aug 27. Review. — View Citation

Fang J. Some anthocyanins could be efficiently absorbed across the gastrointestinal mucosa: extensive presystemic metabolism reduces apparent bioavailability. J Agric Food Chem. 2014 May 7;62(18):3904-11. doi: 10.1021/jf405356b. Epub 2014 Mar 31. Review. — View Citation

González-Barrio R, Borges G, Mullen W, Crozier A. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy. J Agric Food Chem. 2010 Apr 14;58(7):3933-9. doi: 10.1021/jf100315d. — View Citation

González-Barrio R, Edwards CA, Crozier A. Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies. Drug Metab Dispos. 2011 Sep;39(9):1680-8. doi: 10.1124/dmd.111.039651. Epub 2011 May 27. — View Citation

Stalmach A, Edwards CA, Wightman JD, Crozier A. Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans. Mol Nutr Food Res. 2012 Mar;56(3):497-509. doi: 10.1002/mnfr.201100566. Epub 2012 Feb 14. — View Citation

Stalmach A, Edwards CA, Wightman JD, Crozier A. Identification of (poly)phenolic compounds in concord grape juice and their metabolites in human plasma and urine after juice consumption. J Agric Food Chem. 2011 Sep 14;59(17):9512-22. doi: 10.1021/jf2015039. Epub 2011 Aug 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in urinary anthocyanin and ellagitannin metabolite excretion after ingestion of 300g blended raspberries measured by ultra-high performance liquid chromatography-mass spectrometry	All urine excreted for 12 h prior to supplementation was collected as well as that excreted over 48 h after ingestion of raspberries. Urine samples were vortexed, centrifuged at 16110 g for 10 min at 5°C, and passed through 0.45 µm filter discs prior to the analysis of 5 µL aliquots by UHPLC-MS.	baseline excretion (12 h before intervention), and 0-4 h, 4-8 h, 8-24 h, 24-32 h, 32-48 h post ingestion	No
Secondary	Changes in plasma concentration of anthocyanin and ellagitannin metabolites after ingestion of 300g blended raspberries measured by ultra-high performance liquid chromatography-mass spectrometry	Blood samples were collected in heparin tubes before and after raspberry consumption up to 24 h. Plasma samples were vortexed and 400 µL aliquots were mixed with 1 mL of 2% formic acid in acetonitrile. The samples were then vortexed and ultrasonicated for 10 min. After centrifugation at 16110 g for 10 min, supernatants were reduced to dryness in vacuo using a Speedvac concentrator and resuspended in 100 µL of methanol:water:formic acid (50:50:0.1, v/v/v) which was centrifuged at 16100 g for 10 min and 5 µL aliquots of the supernatant analysed by UHPLC-MS.	0 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 24 h post ingestion	No