Relative Oral Bioavailability of GABA From Tomatoes

Plasmakinetics of GABA From Tomatoes as Compared to GABA From a Supplement, After a Single Oral Administration in Healthy Young Men

In this four-way crossover study, a plasmakinetic profile of GABA from tomatoes as compared to a gamma-aminobutyric acid (GABA) supplement in healthy young men will be established. In addition, a plasmakinetic profiles of glutamate from a supplement and from tomatoes as well as the effects of glutamate from tomatoes and a supplement on the GABA plasma levels will be determined. This study will therefore provide information about the effect of a food matrix on GABA plasmakinetics.

Study Overview

• Status: Completed
• Conditions: GABA Plasmakinetics
• Intervention / Treatment: Dietary supplement: Tomato; Dietary supplement: GABA supplement; Dietary supplement: Glutamate supplement

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Wageningen, Netherlands
    • Wageningen University, Division of Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• BMI between 18.5 and 25 kg/m2
• Age is between 18 and 28 years
• Good general health
• Male
• Veins suitable for blood sampling
• Able to speak Dutch

Exclusion Criteria:

• Is currently suffering from a disease including mental disorders
• Has had any gastrointestinal condition/disease within the 3 months prior to the intervention
• Haemoglobin (Hb) level < 8.5 mmol/L
• Has used medication in the two months before and/or during the intervention. Occasional use of NSAIDs or paracetamol (<once a week on average) are is allowed.
• Reported weight loss or weight gain of > 2 kg in the month prior to the intervention
• Use of dietary supplements, 3 weeks before-, or during the intervention.
• Allergic to products that are provided as part of the standardised diet
• Unwilling to consume the products that are part of the standardised diet
• Allergic to tomatoes
• (History of) drug abuse, in this case meaning >1 x per month use of recreational drugs
• Smoking
• Alcohol consumption of >10 standardised glasses per week.
• Not able to refrain from alcohol consumption 2 days before each test day
• Recent or planned blood donation (<3 month prior to first study day or during intervention)
• Personnel of Wageningen University, department of Human Nutrition and Health,
• Currently participating in other research or was participating in another study within 1 month of the intervention or within 3 months if invasive procedures were used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tomato; Single oral administration	Dietary supplement: Tomato; A maximum of 1 kilo pureed tomatoes, containing 1 gram of GABA.
Experimental: GABA supplement; Single oral administration	Dietary supplement: GABA supplement; 1 gram of GABA dissolved in water.; Other Names: Gamma-aminobutyric acid
Experimental: Glutamate supplement; Single oral administration	Dietary supplement: Glutamate supplement; A maximum of 8 grams glutamate, adjusted to amount of glutamate given in the tomato arm. Dissolved in water.
No Intervention: Placebo; Single oral administration, same volume of water that is distributed in the other arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC ) of plasma-time curves of GABA	After intake of a GABA supplement and tomatoes.	6 months
Peak Plasma Concentration (Cmax) of plasma-time curves of GABA	After intake of a GABA supplement and tomatoes.	6 months
Time to Peak Plasma Concentration (Tmax) of plasma-time curves of GABA	After intake of a GABA supplement and tomatoes.	6 months
Half-life (T1/2) of plasma-time curves of GABA	After intake of a GABA supplement and tomatoes.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) of plasma-time curves of glutamate	After intake of a glutamate supplement and tomatoes	6 months
Peak Plasma Concentration (Cmax) of plasma-time curves of glutamate	After intake of a glutamate supplement and tomatoes	6 months
Time to Peak Plasma Concentration (Tmax) of plasma-time curves of glutamate	After intake of a glutamate supplement and tomatoes	6 months
Half-life (T1/2) of plasma-time curves of glutamate	After intake of a glutamate supplement and tomatoes	6 months
Area under the plasma concentration versus time curve (AUC) AUC of plasma-time curves of GABA in response to a glutamate supplement.	This will be compared to the plasma time-curves of GABA after tomato intake.	6 months
Peak Plasma Concentration (Cmax) of plasma-time curves of GABA in response to a glutamate supplement.	This will be compared to the plasma time-curves of GABA after tomato intake.	6 months
Time to Peak Plasma Concentration (Tmax) of plasma-time curves of GABA in response to a glutamate supplement.	This will be compared to the plasma time-curves of GABA after tomato intake.	6 months
Half-life (T1/2) of plasma-time curves of GABA in response to a glutamate supplement.	This will be compared to the plasma time-curves of GABA after tomato intake.	6 months

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Nunhems; Agrico Research; Avebe
• Investigators: Principal Investigator: Renger Witkamp, PhD, Wageningen University

Publications and helpful links

General Publications

• de Bie TH, Balvers MGJ, de Vos RCH, Witkamp RF, Jongsma MA. The influence of a tomato food matrix on the bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate in healthy men. Food Funct. 2022 Aug 15;13(16):8399-8410. doi: 10.1039/d2fo01358d.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): December 5, 2019
• Study Completion (Actual): December 5, 2019

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 17, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Bioavailability; Glutamate; GABA; Tomato; Plasmakinetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Agents; gamma-Aminobutyric Acid
• Other Study ID Numbers: 19/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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