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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03526107
• Other study ID #: 429275-T
• Status: Completed
• Phase: N/A
• Start date: February 16, 2017
• Est. completion date: May 31, 2017

Study information

• Verified date: October 2022
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 31, 2017
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Other:
• CF Control
CF Control: 587 mg of cocoa flavanols, <1 mg caffeine and <1 mg theobromine
• CF-Theobromine
CF-Theobromine: 575 mg of cocoa flavanols, 11 mg caffeine and 93 mg theobromine
• CF-Caffeine
CF-Caffeine: 587 mg of cocoa flavanols, 112 mg caffeine and <1 mg theobromine

Locations

Country	Name	City	State
United States	Ragle Human Nutrition Research Center, Department of Nutrition at UC Davis	Davis	California
United States	UC Davis	Davis	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	Mars, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

Heiss C, Kleinbongard P, Dejam A, Perré S, Schroeter H, Sies H, Kelm M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol. 2005 Oct 4;46(7):1276-83. — View Citation

Koster H, Halsema I, Scholtens E, Knippers M, Mulder GJ. Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. The role of saturation of phenolsulfotransferase. Biochem Pharmacol. 1981 Sep 15;30(18):2569-75. — View Citation

McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21. — View Citation

Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H. Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23. — View Citation

Schroeter H, Heiss C, Spencer JP, Keen CL, Lupton JR, Schmitz HH. Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Aspects Med. 2010 Dec;31(6):546-57. doi: 10.1016/j.mam.2010.09.008. Epub 2010 Sep 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Flavanol metabolites in plasma	Plasma concentration of flavanol metabolites	Before to 6 h post test material intake
Primary	Flavanol metabolites in urine	Amount of flavanols metabolites excreted in urine	12 h before to 24 h post test material intake
Secondary	Methylxanthines in plasma	Plasma concentration of methylxanthines and methylxanthine metabolites	Before to 6 h post test material intake
Secondary	Methylxanthines in urine	Amount of methylxanthines and methylxanthine metabolites excreted in urine	12 h before to 24 h post test material intake