Flavanol Absorption, Metabolism and Excretion From Fruit-based Drinks and Other Food Matrixes

NCT ID: NCT03526094

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-05
• Study Completion Date: 2018-02-09

Brief Summary

Dietary intervention study in healthy adult males to evaluate concentration of flavanol metabolites in plasma and urine after single acute intakes of flavanols from different fruit-based drinks.

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 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 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.

This study consisted of two parts. One part investigated flavanols absorption and metabolism from different fruit-based drinks and other food matrixes. The second part investigated flavanol absorption and metabolism after the intake of a flavanol drink alone and simultaneously consumed with a banana-based drink.

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Flavanols-capsules

Capsules containing 541 mg cocoa flavanols (75 mg epicatechin) and 315 g of milk (1% fat)

Group Type: ACTIVE_COMPARATOR

Flavanols-capsules

Intervention Type: OTHER

Capsules containing 456 mg cocoa flavanols and 315 g of milk (1% fat)

Flavanol-banana blend

Fruit blend prepared by mixing 177 g ripe, frozen bananas, 240 g almond milk and a chocolate flavored powder containing 638 mg cocoa flavanols (88 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-banana blend

Intervention Type: OTHER

Fruit blend prepared by mixing 177 g ripe, frozen bananas, 240 g almond milk and a chocolate flavored powder containing 626 mg cocoa flavanols

Flavanol-high protein drink

Drink prepared by mixing 225 mL of a chocolate flavored high protein dairy drink with a CF powder containing 565 mg cocoa flavanols (78 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-high protein drink

Intervention Type: OTHER

Drink prepared by mixing 225 mL of a chocolate flavored high protein dairy drink with a CF powder containing 533 mg cocoa flavanols

Flavanol-berry blend

Fruit blend prepared by mixing 120 g almond milk, 70 g water, 95 g yogurt, 50 g each strawberries, blueberries, blackberries, raspberries, 105 g crushed ice and a fruit-flavored powder containing 484 mg cocoa flavanols (68 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-berry blend

Intervention Type: OTHER

Flavanol-berry blend prepared by mixing 120 g almond milk, 70 g water, 95 g yogurt, 50 g each strawberries, blueberries, blackberries, raspberries, 105 g crushed ice and a fruit-flavored powder containing 561 mg cocoa flavanols

Flavanol-sports drink

Drink prepared by mixing 488 g of a sports drink with a CF powder containing 565 mg cocoa flavanols (78 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-sports drink

Intervention Type: OTHER

Drink prepared by mixing 488 g of a sports drink with a CF powder containing 533 mg cocoa flavanols

Flavanol-peanut butter toast

Prepared by mixing 32 g peanut butter with a chocolate flavored powder containing 653 mg cocoa flavanols (85 mg epicatechin) and spread on 1 slice toasted bread (50 g) and 50 g sliced strawberries

Group Type: EXPERIMENTAL

Flavanol-peanut butter toast

Intervention Type: OTHER

Prepared by mixing 32 g peanut butter with a chocolate flavored powder containing 602 mg cocoa flavanols and spread on 1 slice toasted bread (50 g) and 50 g sliced strawberries

Flavanol-oats

Prepared by mixing 40 g quick oats with 237 g boiling water and combined with a chocolate flavored powder containing 653 mg cocoa flavanols (85 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-oats

Intervention Type: OTHER

Prepared by mixing 40 g quick oats with 237 g boiling water and combined with a chocolate flavored powder containing 602 mg cocoa flavanols

Flavanol-yogurt

Prepared by 227 g yogurt (0% fat) mixed with a fruit-flavored powder containing 484 mg cocoa flavanols (68 mg epicatechin)

Group Type: EXPERIMENTAL

Flavanol-yogurt

Intervention Type: OTHER

Prepared by 227 g yogurt (0% fat) mixed with a fruit-flavored powder containing 561 mg cocoa flavanols

II- Flavanol drink

Drink prepared by mixing 240 g almond milk with a chocolate flavored powder containing 638 mg cocoa flavanols (88 mg epicatechin)

Group Type: ACTIVE_COMPARATOR

II- Flavanol drink

Intervention Type: OTHER

Drink prepared by mixing 240 g almond milk with a chocolate flavored powder containing 626 mg cocoa flavanols

II- Flavanol drink + banana blend

Drink 1 (Flavanol drink): prepared by mixing 120 g almond milk with 638 mg cocoa flavanols (88 mg epicatechin) Drink 2 (Fruit blend): prepared by mixing 120 g almond milk blended with 177 g ripe, frozen bananas

Group Type: EXPERIMENTAL

II- Flavanol drink + banana blend

Intervention Type: OTHER

Drink 1 (Flavanol drink): prepared by mixing 120 g almond milk with 626 mg cocoa flavanols Drink 2 (Fruit blend): prepared by mixing 120 g almond milk blended with 177 g ripe, frozen bananas

Interventions

Flavanols-capsules

Capsules containing 456 mg cocoa flavanols and 315 g of milk (1% fat)

Intervention Type: OTHER

Flavanol-banana blend

Fruit blend prepared by mixing 177 g ripe, frozen bananas, 240 g almond milk and a chocolate flavored powder containing 626 mg cocoa flavanols

Intervention Type: OTHER

Flavanol-high protein drink

Drink prepared by mixing 225 mL of a chocolate flavored high protein dairy drink with a CF powder containing 533 mg cocoa flavanols

Intervention Type: OTHER

Flavanol-berry blend

Flavanol-berry blend prepared by mixing 120 g almond milk, 70 g water, 95 g yogurt, 50 g each strawberries, blueberries, blackberries, raspberries, 105 g crushed ice and a fruit-flavored powder containing 561 mg cocoa flavanols

Intervention Type: OTHER

Flavanol-sports drink

Drink prepared by mixing 488 g of a sports drink with a CF powder containing 533 mg cocoa flavanols

Intervention Type: OTHER

Flavanol-peanut butter toast

Prepared by mixing 32 g peanut butter with a chocolate flavored powder containing 602 mg cocoa flavanols and spread on 1 slice toasted bread (50 g) and 50 g sliced strawberries

Intervention Type: OTHER

Flavanol-oats

Prepared by mixing 40 g quick oats with 237 g boiling water and combined with a chocolate flavored powder containing 602 mg cocoa flavanols

Intervention Type: OTHER

Flavanol-yogurt

Prepared by 227 g yogurt (0% fat) mixed with a fruit-flavored powder containing 561 mg cocoa flavanols

Intervention Type: OTHER

II- Flavanol drink

Drink prepared by mixing 240 g almond milk with a chocolate flavored powder containing 626 mg cocoa flavanols

Intervention Type: OTHER

II- Flavanol drink + banana blend

Drink 1 (Flavanol drink): prepared by mixing 120 g almond milk with 626 mg cocoa flavanols Drink 2 (Fruit blend): prepared by mixing 120 g almond milk blended with 177 g ripe, frozen bananas

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Mars, Inc.

INDUSTRY

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carl L Keen, PhD

Role: PRINCIPAL_INVESTIGATOR

UC Davis

Javier I Ottaviani, PhD

Role: STUDY_DIRECTOR

Mars, Inc.

Locations

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

Davis, California, United States

UC Davis

Davis, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20854838 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22240152 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 6946775 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16794446 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16198843 (View on PubMed)

Other Identifiers

429275-D

Identifier Type: -

Identifier Source: org_study_id