Intake-dependent Effect of Cocoa Flavanol Absorption, Metabolism and Excretion in Humans
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Healthy
- Sponsor
- University of California, Davis
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Change in levels of gut microbiome derived metabolites in urine
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
A randomized, double-masked and cross-over dietary intervention study in healthy young adult males to evaluate the concentration of F-derived metabolites in plasma and urine after single acute intakes of F-containing drinks on four different test days.
Detailed Description
Flavanols (F) are plant-derived compounds commonly present in the human diet. Examples of F-containing foods and beverages are apples, chocolate, tea, wine, berries, pomegranate and nuts. The consumption of F-containing foods and beverages has been associated with improvements in cardiovascular health. In this context, there exists a great interest in describing the absorption, metabolism and excretion of F in humans, as it is thought that F-derived metabolites present in circulation are the mediators of F-beneficial effects in humans. Recently, we described a series of F-derived metabolites in circulation that are present after the consumption of a single acute intake amount of F in humans. A key question, however, is if the metabolites we observed after a single acute feeding are the same as those that occur in individuals who consume F-rich diets on a regular basis. Studies investigating the metabolism of numerous other xenobiotics have shown that the profile of metabolites can greatly vary over time, as well as with the amount of xenobiotic ingested. In this context, and considering that i) the amount of F-consumed from diet greatly varies among individuals, ii) recent epidemiology studies indicate that the vascular protective effects of F diets primarily occur when daily intake of F are relatively high; and iii) there is evidence of an intake amount-dependency on the vascular effects of F in dietary intervention studies; we submit it is important to assess whether or not there are F intake amount-dependent effects on the levels and profile of F-derived metabolites in humans. This study will provide new information concerning the F-derived metabolites that may be responsible for mediating F-beneficial effects in humans. We suggest the information that will be obtained from the outlined work will be particularly timely given ongoing discussion concerning the possible generation of dietary recommendations for F-rich foods.
Investigators
Eligibility Criteria
Inclusion Criteria
- •No prescription medications
- •BMI 18.5 - 29.9 kg/m2
- •Weight ≥ 110 pounds
- •previously consumed cocoa and peanut products, with no adverse reactions
Exclusion Criteria
- •Adults unable to consent
- •Prisoners
- •Non-English speaking\*
- •BMI ≥ 30 kg/m2
- •Allergies to nuts, cocoa and chocolate products
- •Active avoidance of coffee and caffeinated soft drinks
- •Under current medical supervision
- •A history of cardiovascular disease, stroke, renal, hepatic, or thyroid disease
- •History of clinically significant depression, anxiety or other psychiatric condition
- •History of Raynaud's disease
Outcomes
Primary Outcomes
Change in levels of gut microbiome derived metabolites in urine
Time Frame: Urine collected 12h previous to intervention and up to 24 h after intervention
Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone metabolites
Change in levels of gut microbiome derived metabolites in plasma
Time Frame: Plasma collected before (0h) and up to 6h post intervention
Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone
Change in levels of structurally related epicatechin metabolites in urine
Time Frame: Urine collected 12h previous to intervention and up to 24 h after intervention
Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin
Change in levels of structurally related epicatechin metabolites in plasma
Time Frame: Plasma collected before (0h) and up to 6h post intervention
Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin
Secondary Outcomes
- Composite of pharmacokinetic (PK) parameters of metabolites Elimination Rate Constant(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Volume of Distribution(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Maximum Plasma Concentration (CMax)(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Time to Maximum Plasma Concentration(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve extrapolated to infinity(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Elimination Half-Life(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Systemic Clearance(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites Renal Clearance(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Feces(Before intervention (0h) and up to 24 h after intervention)
- Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Urine(Before intervention (0h) and up to 24 h after intervention)