Absorption, Metabolism and Excretion of Apigenin and Apigenin Glycosides

Probe dietary intervention study in healthy young adult males to evaluate the concentration of apigenin derived metabolites in plasma and urine after single acute intakes of different apigenin-containing test materials.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Chamomile Tea; Other: Parsley based drink; Other: Parsley Yogurt; Other: Apigenin; Other: Parsley-based drink (II)

Detailed Description

Flavonoids, including the sub groups of Flavones (FO) are plant-derived compounds commonly present in the human diet. Examples of FO-containing foods and beverages are parsley, celery, and chamomile. The study described below will provide initial information of apigenin derived metabolites in humans. The investigators suggest the information that will be obtained from the outlined work will be particularly timely given increasing interest in the putative health effects of FO intake in humans.

This study consisted of two parts. The first part consisted of a probe study in which the investigators investigated the absorption and metabolism from four flavone-containing test products. The second phase investigated absorption and metabolism after the intake of a flavone-containing parsley drink.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Davis, California, United States, 95616
      • UC Davis
    • Davis, California, United States, 95616
      • Ragle Human Nutrition Research Center, Department of Nutrition at UC Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 metabolic equivalence of task (MET) as defined by Centers for Disease Control and Prevention (CDC) and American College of Sports Medicine (ACSM) guidelines) 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chamomile Tea; Chamomile Tea in 300mL hot water	Other: Chamomile Tea; Chamomile Tea in 300mL hot water
Experimental: Parsley based drink; 3.2 g dried parsley in 300mL hot water	Other: Parsley based drink; 3.2 g dried parsley in 300mL hot water
Experimental: Parsley Yogurt; 3.2 g dried parsley in 100g plain yogurt	Other: Parsley Yogurt; 3.2 g dried parsley in 100g plain yogurt
Experimental: Apigenin; Apigenin capsule mixed with 300mL hot water	Other: Apigenin; Apigenin capsule mixed with 300mL hot water
Experimental: Parsley-based drink (II); 3.2 g of dried parsley in 300 ml of hot water	Other: Parsley-based drink (II); 3.2 g dried parsley in 300mL hot water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flavone metabolites in plasma	Concentration of flavone metabolites in plasma	before to 6 h post test material intake
Flavone metabolites in urine	Amount of flavone metabolites excreted in urine	12 h before to 24 h post test material intake

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Mars, Inc.

Publications and helpful links

General Publications

• Heiss C, Kleinbongard P, Dejam A, Perre 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. doi: 10.1016/j.jacc.2005.06.055.
• 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.
• 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.
• 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. doi: 10.1016/0006-2952(81)90584-0. No abstract available.
• 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. doi: 10.1097/00005344-200606001-00003.
• Borges G, Fong RY, Ensunsa JL, Kimball J, Medici V, Ottaviani JI, Crozier A. Absorption, distribution, metabolism and excretion of apigenin and its glycosides in healthy male adults. Free Radic Biol Med. 2022 May 20;185:90-96. doi: 10.1016/j.freeradbiomed.2022.04.007. Epub 2022 Apr 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2015
• Primary Completion (Actual): July 30, 2016
• Study Completion (Actual): July 30, 2016

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2019
• Last Update Submitted That Met QC Criteria: May 21, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: chamomile; polyphenols; ADME; flavone; apigenin; parsley
• Other Study ID Numbers: 429275-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Only researchers listed in the protocol and approved by the IRB will have access to IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No