Lycopene and Beta-carotene Metabolism in the Digestive Tract of Healthy Men

NCT ID: NCT03492593

Last Updated: 2018-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2016-03-31

Brief Summary

Consumption of foods containing carotenoids, as well as vitamin E, have been associated with lower risk of developing a number of chronic diseases. While the parent compounds have largely been assumed to exert protective antioxidant effects, more recent work has suggested that metabolites may be bioactive. Very little attention has been given to the metabolism of these compounds during the digestive process. Our primary aim is to conduct a postprandial feeding study in healthy men to determine the stability of carotenoids and vitamin E during digestion, and to identify the primary metabolites produced in various compartments of the upper gastrointestinal tract and blood during digestion. Targeted metabolites will be identified and quantitated using high-performance liquid chromatography-tandem mass spectrometry methods previously developed. In addition, a non-targeted metabolomics approach will be used to identify non-predicted metabolites in the samples. A better understanding of carotenoid and vitamin E stability and metabolism during digestion will provide greater insight into how these compounds may confer protection against chronic disease.

Detailed Description

Consumption of foods containing the carotenoids lutein, lycopene, beta-carotene, as well as vitamin E, have been associated with lower risk of developing chronic diseases including cardiovascular disease, cancer, age related macular degeneration, and cognitive decline. While the parent compounds have largely been assumed to exert protective antioxidant effects, more recent work has suggested that metabolites may be bioactive. Very little attention has been given to the metabolism of these compounds during the digestive process. Our primariy aim is to conduct a postprandial feeding study in healthy men to determine the stability of carotenoids and vitamin E during digestion, and to identify the primary metabolites produced in the upper gastrointestinal tract during digestion. Subjects will be fed a meal containing either lutein,lycopene, deuterated beta-carotene, or deuterated vitamin E. Gastric and duodenal samples will be taken 5 hours post-meal consumption, while blood plasma and chylomicron fractions will be taken over 7 hours post-meal consumption. Targeted metabolites will be identified and quantitated using high-performance liquid chromatography-tandem mass spectrometry methods previously developed. In addition, a non-targeted metabolomics approach will be used to identify non-predicted metabolites in a subset of collected samples. Overall, this research will provide very original insight about carotenoid and vitamin E metabolites produced during the digestive process and their absorption by the human body. This information is essential to understand how these compounds may confer protection against chronic disease.

Conditions

Digestion Chambers; Stability and Metabolism of Carotenoids and Vitamin E

Study Design

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

Study Groups

lycopene

A dose of lycopene (20 mg) is provided as part of an emulsified liquid meal (with or without 160 mg powdered ferrous sulfate). Samples from the upper digestive tract (gastric or duodenal) are aspirated over 4 hours, and blood collected over 7 hours. Blood plasma and chylomicron fractions isolated. The subject returns for 3 additional visits with 2 weeks between each visit. The same protocol is followed, with the subject receiving all combinations of meal (w/ and w/o iron) and upper digestive tract sampling (gastric or duodenal)

Group Type: EXPERIMENTAL

lycopene

Intervention Type: OTHER

A tomato oleoresin containing lycopene

13C beta-carotene

A dose of 13C beta-carotene (20 mg) is provided as part of an emulsified liquid meal. Samples from the upper digestive tract (gastric or duodenal) are aspirated over 5 hours, blood collected over 7 hours, and urine collected over 7 hours. Blood plasma and chylomicron fractions isolated. The subject returns for 1 additional visit with a minimum of 4 weeks between each visit. The same protocol is followed, with sampling taken from the remaining upper digestive tract compartment (gastric or duodenal)

Group Type: EXPERIMENTAL

beta-carotene

Intervention Type: OTHER

13C beta-carotene

control

The same procedure is followed (as detailed in the experimental arms) but the subject receives an emulsified liquid meal without carotenoids or vitamin E.

Group Type: PLACEBO_COMPARATOR

control

Intervention Type: OTHER

emulsified liquid meal alone

Interventions

lycopene

A tomato oleoresin containing lycopene

Intervention Type: OTHER

beta-carotene

13C beta-carotene

Intervention Type: OTHER

control

emulsified liquid meal alone

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• BMI of 18-29.9
• Cholesterol < 2.2 g/L
• Triglycerides < 1.5 g/L
• Blood sugar </= 1.1 g/L
• Hemoglobin > 13 g/dL
• Test negative for hepatitis B, C, and HIV

Exclusion Criteria

• Hepatitis B and C
• HIV
• Blood donation or blood sampling less than 2 months prior to the first daylong study day
• Craniofacial trauma
• Smokers
• Regular consumption of vitamins or supplements rich in carotenoids or vitamin E in the past 3 months
• Alcohol consumption > 140 g per week (equivalent to 14 glasses of wine, 14 glasses of beer (25 mL), or 14 shots of liquor).
• Past or present eating disorder (anorexia, bulimia, etc.)
• Food allergies to components of the liquid test meal
• Medical treatment or surgical intervention affecting the digestive tract or function of the digestive tract
• Metabolic disorders (disorder of the liver or pancreas, diabetes, hemochromatosis, gastro-intenstinal disorders with the exception of appendicitis)
• Use of certain medications (those which regulate intestinal transit, those which reduce blood lipids and cholesterol, those which interact with bile salts)
• Intense physical activity > 4 1/2 hours per week
• Participation in another clinical study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Aix Marseille Université

OTHER

Sponsor Role: collaborator

Hôpital de la Conception

UNKNOWN

Sponsor Role: collaborator

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

OTHER

Sponsor Role: lead

Responsible Party

Patrick Borel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Borel, PhD

Role: PRINCIPAL_INVESTIGATOR

INRA/INSERM/Université Aix-Marseille

Catherine Caris-Veyrat

Role: STUDY_DIRECTOR

INRA/Université d'Avignon

Locations

Centre d'Investigation Clinique de la Hôpital Conception

Marseille, , France

Countries

France

References

Kopec RE, Caris-Veyrat C, Nowicki M, Gleize B, Carail M, Borel P. Production of asymmetric oxidative metabolites of [13C]-beta-carotene during digestion in the gastrointestinal lumen of healthy men. Am J Clin Nutr. 2018 Oct 1;108(4):803-813. doi: 10.1093/ajcn/nqy183.

Reference Type: DERIVED

PMID: 30256893 (View on PubMed)

Other Identifiers

2013-A01398-37

Identifier Type: REGISTRY

Identifier Source: secondary_id

2013-A01398-37

Identifier Type: -

Identifier Source: org_study_id