Individual Variability in (Poly)Phenol Metabolism, Cardiometabolic Health
Conditions
Keywords
intervention study, (poly)phenols, metabolic phenotypes, metabotypes, cardiometabolic diseases, inter-individual variability, phenolic metabolites
Brief summary
The study is a single-dose acute clinical trial aiming at identifying aggregate metabolic phenotypes for the main dietary (poly)phenols and assessing the factors associated with their formation. The treatment consists of a nutritional challenge representative of the consumption of (poly)phenols in Europeans (so-called oral (poly)phenol challenge test, OPCT) and foresees the supplementation of three standardized tablets rich in (poly)phenols, prepared from various commercially available plant extracts constituting sources of specific (poly)phenols. Urinary excretion of (poly)phenol metabolites will be evaluated at 24 hours after tablet consumption or, for two subgroups of volunteers, at different time points for 24 hours upon tablet consumption. Blood pressure and heart rate will also be measured and anthropometric data collected. Information will be collected on genetic polymorphisms related to the metabolism of (poly)phenols, gene expression, standard cardiometabolic health biomarkers, cardiometabolic risk scores and gut microbiota profile, through the collection of urine, blood and stool samples. Volunteers will follow a (poly)phenol-free diet before and after the OPCT. To check compliance with food restrictions, a 24-hour recall will be carried out on each visit. For a sub-group of 50 subjects, 3 months after the first challenge, the OPCT will be repeated with further urinary and fecal collection.
Interventions
DIETARY_SUPPLEMENTOral (poly)phenol challenge test (OPCT)
Nutritional challenge with standardized (poly)phenol-rich tablets
Sponsors
Azienda Ospedaliero-Universitaria di Parma
University of Birmingham
National Research Council, Spain
University of Parma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult (18-74 y) * BMI 18.5-35 kg/m\^2
Exclusion criteria
* Past cardiovascular events and metabolic diseases including diabetes * Inflammatory bowel diseases or gastro-intestinal surgery * Renal (GFR\<60 ml/min) or hepatic diseases (liver enzymes \>2.5 fold higher) * Immunodeficiency or autoimmune diseases (other than well-compensated hypothyroidism) * Mental disorders * Antibiotic therapy within the last month * Food allergies * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of aggregate phenolic metabotypes | 24 hours post-consumption | Assessing the variability in the urinary excretion of phenolic metabolites among volunteers after consumption of (poly)phenol-rich tablets by using data-driven clustering. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessing risk prediction scores | Baseline | Risk prediction scores (i.e., Framingham General Cardiovascular Risk Score, Framingham Heart Study Primary Risk Functions for heart disease, stroke, diabetes, fatty liver disease, and hypertension, Atherosclerotic Cardiovascular Disease (ASCVD) Risk, QRISK3®, QDScore®, Finnish Diabetes Risk Score (FINDRISC)) will be assessed to understand their relationship with the aggregate phenolic metabotypes observed. The higher the scores, the worse the risk of developing the disease. |
| Evaluating trimethylamine N-oxide (TMAO) in urine and plasma samples | Baseline | TMAO will be quantified in baseline urine and fasting plasma samples by UHPLC-MS/MS. |
| Evaluating eicosanoids in urine samples | Baseline | Eicosanoids, including prostaglandins, thromboxanes, leukotrienes, isoprostanes and neuroprostanes will be evaluated in baseline urine samples (0-h) by UHPLC-QqQ-MS/MS. |
| Assessing DNA oxidation catabolites and branched fatty acyl esters of hydroxyl fatty acids (FAHFAs) in plasma samples | Baseline | DNA oxidation catabolites and FAHFAs will be measured in fasting plasma samples by UHPLC-QqQ-MS/MS. |
| Determining genetic differences among subjects | Baseline | Genotyping will be conducted using genome wide, SNP array approach untargeted methodology, using commercially available SNP arrays and a tSNP approach. This approach will involve the genotyping of approximately 300 SNPs. Genomic DNA will be prepared from PBMCs isolated from blood samples. |
| Assessing transcriptomic signatures in peripheral blood mononuclear cells (PBMCs). | Baseline | Specific patterns of gene expression related to each metabotype will be investigated in PBMCs by using a microarray-based approach. Analysis will be carried out in a subset of 10 samples for each metabotype. |
| Assessing common cardiometabolic health biomarkers in blood samples | Baseline | Samples will be processed for the analysis of common biomarkers of cardiometabolic health: total cholesterol (mg/dL), HDL-cholesterol (mg/dL), triglycerides (mg/dL), glucose (mg/dL), insuline (uUI/mL). Analyses will follow standardised routine procedures. |
| Assessing dietary habits | Baseline | Dietary habits will be assessed through a food frequency questionnaire. |
| Assessing anthropometric measurements | Baseline | Weight and height will be combined to report BMI in kg/m\^2 and this will be carried out according to standardized procedures. Waist circumference and hip circumference, waist-to-height ratio, waist-to-hip ratio, and body composition measurement (skinfold test and bioelectrical impedance analysis). |
| Assessing blood pressure and heart rate | Baseline | Systolic and diastolic blood pressure and heart rate of each volunteer will be obtained after a 5-min rest in a seated position in the baseline visit. |
| Evolution over the time of the phenolic metabolites in urine samples | Different collection times for 24 hours (0; 0-3; 3-6; 6-9; 9-12; 12-24; 24 h) | Assessed by using UHPLC-MS/MS for individual detection and quantification. |
| Untargeted urinary metabolomics | Baseline and 24 hours post-consumption | The untargeted LC-IMS-MS metabolomics approach will allow to assess potential differences among the metabolomes of individuals belonging to different aggregate phenolic metabotypes. |
| Assessing the stability of aggregate phenolic metabotypes among individuals after 3 months | 24 hours post-consumption in a test carried out after 3 months after the first supplementation | Assessing the variability in the urinary excretion of phenolic metabolites among volunteers after consumption of (poly)phenol-rich tablets, considering the metabotype to which each volunteer belongs to once the volunteer re-do the oral (poly)phenol challenge test after 3 months from the first supplementation. |
| Determining gut microbiota composition and functionality in fecal samples | Baseline | Microbial profiling will be assessed by shallow shotgun metagenomics. Full shotgun metagenomics analysis will be carried out to determine functional pathways in a sample subset (50 samples). |
Countries
Italy
Outcome results
None listed