An Acute Human Intervention With Flavonoid to Investigate Absorption, Metabolism and Excretion

NCT01922869 | Unknown

• 1 other identifier: R21072
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The era of general dietary recommendations for the whole population may be coming to an end, as it is becoming apparent that we are all unique and do not respond in the same way to the same foods. Within a decade it is believed that doctors will be able to take profiles of their patients, identify specific diseases for which they are at risk and create personalised nutrition plans accordingly. At the University of East Anglia, UK the investigators are interested in particular food compounds known as flavonoids which can be found in foods such as chocolate, orange juice and blackberries (COB). The study will determine if factors such as age, gender, genetics and the bacteria present in our guts contribute to variability between individuals in their absorption, metabolism and excretion of flavonoids.

Conditions

Pharmacokinetics of Flavonoids in Humans

Keywords

Absorption; Metabolism; Excretion; Flavonoids; Polyphenols; Genes; Gut-microflora

Outcome Measures

Primary Outcomes (2)

• Flavanoid metabolites

  Concentrations of flavonoid metabolites will be assessed using state-of-the-art liquid chromatography-tandem mass spectrometry (LC-MS/MS) and quantified against commercially available standards. Serum and urine will be acidified and then extracted by solid phase extraction (SPE). Metabolite identification will be performed using a QTrap 4000 linear ion trap mass spectrometer (ABSciex, Canada) by multi-reaction monitoring (MRM) optimized for the detection of pure standards. Metabolites will be confirmed on the basis of retention time and parent-daughter ion fragmentation transitions.

  12 months

• Genes involved in flavonoid metabolism

  Candidate genes encoding proteins involved in the flavonoid metabolism pathway will be identified from the literature and available pathway databases such as gene ontology, gene network, KEGG. Putative functional SNPs within these genes will be identified from the literature and/or online tools such genepipe and polyphen. In addition tag SNPs will be identified across the selected genes. This approach will involve the genotyping of approximately 200 single nucleotide polymorphisms (SNPs). Genotyping of these SNPs will be performed with the MassARRAY and iPlex systems of the Sequenom genotyping platform (Sequenom, San Diego, CA), which uses the MALDITOF primer extension assay. The associations of these SNPs and flavonoid metabolism will them be investigated.

  12 months

Secondary Outcomes (1)

• Effect of gut microbiota on flavonoid metabolism

  18 months

Study Arms (1)

COB mixture

EXPERIMENTAL

One time ingestion of flavonoid mixture from chocolate (80 g), orange juice (500 ml)and blackberries (160 g), also known as the 'COB mixture' providing approximately 640 mg of flavan-3-ols, 390 mg of anthocyanins and 342 mg of flavanones respectively.

Dietary Supplement: Flavonoids

Interventions

Flavonoids DIETARY_SUPPLEMENT

COB mixture

Eligibility Criteria

• Age: 18 Years - 77 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female
• Caucasian of European origin
• Age either between 18-30 years or between 65-77 years

You may not qualify if:

• BMI \< 18.5 kg/m2 or BMI \> 30 kg/m2
• Smokers or nicotine users
• High (above 140/90 mmHg ) or low (less than 90/60 mmHg) blood pressure
• Having any existing medical conditions or significant past medical history likely to affect study measurements e.g., type 2 diabetes, cardiovascular, renal, liver or gastrointestinal diseases
• Unsatisfactory biochemical, haematological or urinary assessment, indicating abnormal; renal or liver function, full blood profile, impaired glucose handling, deranged lipids or measurements considered to be counter indicative of the study by the clinical advisor
• Taking any prescribed medication that could interact with the enzymes involved in the metabolism of flavonoids
• Taking flavonoid containing supplements or other dietary supplements for one month prior to the study (and duration of the study intervention)
• Known allergies to the intervention foods
• Consume more alcoholic beverages on average than 21 units/wk for men, or 14 units/wk for women (The UK Department of Health recommendations)
• Pregnant, breast feeding, or planning a pregnancy (or having fertility treatment)
• Unable to provide informed consent to participate in the study

Sponsors & Collaborators

• University of East Anglia: lead
• Fred Hutchinson Cancer Center: collaborator
• University of Washington: collaborator

Study Sites (1)

Department of Nutrition, University of East Anglia

Norwich, Norfolk, NR4 7TJ, United Kingdom

RECRUITING

Related Publications (1)

• Kay CD, Tejera N, Jennings A, Haldar S, Diment BC, Bevan D, Crossman LC, Li S, Cassidy A, Minihane AM. Effect of age and sex on the urinary elimination of a single dose of mixed flavonoids: results from a single-arm intervention in healthy United Kingdom adults. Am J Clin Nutr. 2025 Jul;122(1):101-111. doi: 10.1016/j.ajcnut.2025.05.006. Epub 2025 May 12.

  PMID: 40368267 DERIVED

MeSH Terms

Interventions

Flavonoids

Intervention Hierarchy (Ancestors)

Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Anne-Marie Minihane, PhD

  Department of Nutrition, University of East Anglia, Norwich, U.K.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sumanto Haldar, PhD

CONTACT

+44-1603591949; S.Haldar@uea.ac.uk

Anne-Marie Minihane, PhD

CONTACT

+44-1603592389; A.Minihane@uea.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: August 14, 2013
• Study Start: July 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 14, 2013

Record last verified: 2013-08

Locations

GB (1)