Pharmacokinetics of Flavonoids in Humans
Conditions
Keywords
Absorption, Metabolism, Excretion, Flavonoids, Polyphenols, Genes, Gut-microflora
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.
Detailed description
The study will recruit men and women who are aged either 18-30 or 65-77 years and are generally healthy.On arriving at the study day we will collect a blood sample. Breakfast will then be supplied in the form of a food or drink that will contain freezedried powder from orange juice, chocolate and blackberry. After breakfast further blood samples will be taken at several time points throughout the day. Urine and faeces samples will also be collected. These biological samples will be tested for flavonoid absorption, metabolism and excretion as well as influence of genetic make-up of individuals and the gut microflora harboured in faecal samples.
Interventions
DIETARY_SUPPLEMENTFlavonoids
Sponsors
Fred Hutchinson Cancer Center
University of Washington
University of East Anglia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 77 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or Female * Caucasian of European origin * Age either between 18-30 years or between 65-77 years
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flavanoid metabolites | 12 months | 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. |
| Genes involved in flavonoid metabolism | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of gut microbiota on flavonoid metabolism | 18 months | We will determine the effects of gut-microbiota variation on flavonoid metabolism. To do this, we will collect faecal samples and determine gut-microflora using faecal bacterial phylogenetic analysis using PCR to amplify 16S rDNA genes. |
Countries
United Kingdom
Contacts
Primary ContactSumanto Haldar, PhD
Backup ContactAnne-Marie Minihane, PhD
Outcome results
None listed