Relative oral bioavailability of GABA from tomatoes

Rationale: Next to its role as a neurotransmitter, GABA has been identified as potential bioactive food component. It is abundantly present in for example certain varieties of potato and tomato. Animal studies show beneficial effects of orally administered GABA in relation to diabetes development and hypertension. Since tomatoes and potatoes are frequently consumed by the Dutch (and other nationalities), these products could potentially be used to substantially increase the GABA intake. However, this depends on the assumption that GABA is effectively absorbed from a food matrix. We expect that the food matrix changes the bio-accessibility and bio-availability of GABA; a food matrix can entrap nutrients or protect them from degradation for example. From literature, it is known that GABA is rapidly absorbed from a supplement but the bioavailability of GABA from a food matrix has not previously been investigated.

Objective: This study aims to establish a plasmakinetic profile of GABA from tomatoes in healthy men and compare it to the kinetic profile of GABA from a supplement. In addition, the effects of glutamate (precursor of GABA) on the plasma-time curves of GABA will be studied.

Study design: This study has a placebo controlled randomized four-way crossover design, with four test days with a minimum of 1 week washout in between.

Study population: 12 subjects, all healthy young men.

Intervention: On a test day, the research subjects will consume either tomatoes with 1 gram of GABA, a dose of 1 gram GABA supplement, a glutamate supplement with a maximum dose of 8 grams or a placebo.

Main study parameters/endpoints: The main study outcome is the plasma-time curve of GABA. This will be evaluated using descriptive kinetics: maximum peak height (Cmax), time-to-peak (Tmax), and area-under-the-curve (AUC).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: GABA and glutamate are naturally present in our diet and are generally recognised as safe for use as a food ingredient by the FDA. In human intervention studies, oral ingestion of GABA or glutamate does not lead to severe adverse events. Some temporary minor adverse events, like nausea, did occur. Therefore, the research subjects in this study might also experience these temporary effects. In addition, the research subjects are required to visit the university a total of 14 times and during the blood sampling they are required to remain at the research facilities. On the test days, the research subjects arrive in a fasted state and remain fasted until 4 hours after intake of the test product. The placement of venous catheters and blood sampling will also lead to mild discomfort. Research subjects do not directly benefit from the intervention but contribute to scientific research and receive a financial compensation of €470,- when completing the whole study.

This study aims to establish a plasmakinetic profile of GABA from tomatoes in healthy men and compare it to the kinetic profile of GABA from a supplement. In addition, the effects of glutamate (precursor of GABA) on the plasma-time curves of GABA will be studied. We hypothesize that a food matrix will affect the plasmakinetics of GABA.

For the study, research subjects will visit the university on four test days separated by a wash out period of one week.

Tomatoes, GABA supplement, Glutamate supplement, Placebo