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Food Matrix Effect on Flavanol Absorption, Metabolism and Excretion: Methylxanthines

Not Applicable
Completed
Conditions
Healthy
Interventions
Other: CF-Theobromine
Other: CF Control
Other: CF-Caffeine
Registration Number
NCT03526107
Lead Sponsor
University of California, Davis
Brief Summary

Dietary intervention study in healthy young adult males to evaluate concentration of flavanol metabolites in plasma and urine after single acute intakes of methylxanthines.

Detailed Description

Flavonoids, including the sub groups of 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, the investigators 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 as well as F-metabolites derived from the metabolic activity of the gut microbiome. A key question, however, is if the metabolites the investigators 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 the xenobiotic ingested. In this context, the investigators submit it is important to assess whether or not there are food matrix-dependent effects on the levels and profile of F-derived metabolites in humans. The investigators 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 and increasing interest in the putative health effects of F intake in humans.

Following the beginning of the trial, an advanced method to analyze cocoa flavanols was accredited by AOAC International as a First Action Official Method of Analysis https://doi.org/10.1093/jaoacint/qsaa132). This updated method relies on a reference material (RM8403) recently standardized and made commercially available by the U.S. National Institute of Standards and Technology. While the actual cocoa flavanol content of our intervention remained unchanged throughout the trial, the application of this new analytical method led to expected changes in how the total cocoa flavanol content is now reported. Applying AOAC 2020.05/RM8403 to our intervention, the total cocoa flavanol content of select arms in our trials have been updated accordingly.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
10
Inclusion Criteria
  • No prescription medications
  • BMI 18.5 - 29.9 kg/m2
  • Weight ≥ 110 pounds
  • previously consumed cocoa, peanut, parsley, celery and chamomile products with no adverse reactions
Exclusion Criteria
  • Adults unable to consent
  • Prisoners
  • Non-English speaking*
  • BMI ≥ 30 kg/m2
  • Performing vigorous physical activity (i.e. more than 6 MET; metabolic equivalence of task as defined by CDC and ACSM guidelines (http://www.cdc.gov/physicalactivity/everyone/glossary/index.html#vig-intensity; and http://www.cdc.gov/nccdphp/dnpa/physical/pdf/PA_Intensity_table_2_1.pdf ) for more than 3 days a week.
  • Dietary allergies including those to nuts, cocoa and chocolate products, parsley, celery and chamomile.
  • 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
  • History of difficult blood draws
  • Indications of substance or alcohol abuse within the last 3 years
  • Current use of herbal, plant or botanical supplements (multi-vitamin/mineral supplements are allowed)
  • Blood Pressure > 140/90 mm Hg
  • GI tract disorders, previous GI surgery (except appendectomy)
  • Self-reported malabsorption (e.g. difficulty digesting or absorbing nutrients from food, potentially leading to bloating, cramping or gas)
  • Diarrhea within the last 3 months, or antibiotic intake within the last 3 months
  • Vegetarian, Vegan, food faddists, individuals using non-traditional diets, on a weight loss diet or individuals following diets with significant deviations from the average diet
  • Metabolic panel and cholesterol results or complete blood counts that are outside of the normal reference range and are considered clinically relevant by the study physician
  • Cold, flu, or upper respiratory condition at screening
  • Currently participating in a clinical or dietary intervention study

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
CF-TheobromineCF-TheobromineCF-Theobromine: 575 mg of cocoa flavanols (102 mg epicatechin), 11 mg caffeine and 93 mg theobromine
CF ControlCF ControlCF Control: 587 mg of cocoa flavanols (101 mg epicatechin), \<1 mg caffeine and \<1 mg theobromine
CF-CaffeineCF-CaffeineCF-Caffeine: 587 mg of cocoa flavanols (101 mg epicatechin), 112 mg caffeine and \<1 mg theobromine(Experimental)
Primary Outcome Measures
NameTimeMethod
Flavanol metabolites in urine12 h before to 24 h post test material intake

Amount of flavanols metabolites excreted in urine

Flavanol metabolites in plasmaBefore to 6 h post test material intake

Plasma concentration of flavanol metabolites

Secondary Outcome Measures
NameTimeMethod
Methylxanthines in urine12 h before to 24 h post test material intake

Amount of methylxanthines and methylxanthine metabolites excreted in urine

Methylxanthines in plasmaBefore to 6 h post test material intake

Plasma concentration of methylxanthines and methylxanthine metabolites

Trial Locations

Locations (2)

Ragle Human Nutrition Research Center, Department of Nutrition at UC Davis

🇺🇸

Davis, California, United States

UC Davis

🇺🇸

Davis, California, United States

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