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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
14
Fruit-flavored non-dairy drink containing 100 cocoa flavanols/70kg BW.
Fruit-flavored non-dairy drink containing 200 cocoa flavanols/70kg BW.
Fruit-flavored non-dairy drink containing 400 cocoa flavanols/70kg BW.
UC Davis
Davis, California, United States
Change in levels of gut microbiome derived metabolites in urine
Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone metabolites
Time frame: Urine collected 12h previous to intervention and up to 24 h after intervention
Change in levels of gut microbiome derived metabolites in plasma
Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone
Time frame: Plasma collected before (0h) and up to 6h post intervention
Change in levels of structurally related epicatechin metabolites in urine
Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin
Time frame: Urine collected 12h previous to intervention and up to 24 h after intervention
Change in levels of structurally related epicatechin metabolites in plasma
Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin
Time frame: Plasma collected before (0h) and up to 6h post intervention
Composite of pharmacokinetic (PK) parameters of metabolites Maximum Plasma Concentration (CMax)
PK parameters: Cmax: maximum observed concentration in plasma;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Time to Maximum Plasma Concentration
tmax: time to maximum concentration in plasma;
Time frame: Before intervention (0h) and up to 24 h after intervention
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Fruit-flavored non-dairy drink containing 1000 cocoa flavanols/70kg BW.
Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve
AUC0-t: area under the plasma concentration-time curve from hour 0 to the last measurable concentration in plasma;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve extrapolated to infinity
AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Elimination Rate Constant
λZ: apparent terminal elimination rate constant in plasma;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Elimination Half-Life
t1/2: apparent terminal elimination half-life in plasma;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Systemic Clearance
CL/F: systemic clearance;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Renal Clearance
CLR: renal clearance;sampling interval and the total interval examined;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Feces
Aef(0-t): Cumulative amount excreted in the feces over each sampling interval and the total interval examined.
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites Volume of Distribution
Vd/F: apparent volume of distribution;
Time frame: Before intervention (0h) and up to 24 h after intervention
Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Urine
Aeu(0-t): cumulative amount excreted in the urine over each
Time frame: Before intervention (0h) and up to 24 h after intervention