Project

GABA for health – exploring the absorption and metabolic effects of gamma-amino butyric acid

Gamma-amino butyric acid, also know as GABA, is an important neurotransmitter in the (human) brain. GABA receptors have also been found on tissues that are important for glucose homeostasis, such as the pancreas. It has therefore been hypothesized that GABA could be an important regulator of glucose homeostasis, and that GABA supplementation may have beneficial effects in diabetes. Animal studies have shown promising results, but data from human intervention studies using GABA supplements are lacking. Interestingly, GABA is also present in certain plants, such as tomatoes and potatoes, and these foods may also contribute to GABA intake. In this collaborative project between the Nutritional Biology group, Wageningen Plant Research, and tomatoe and potatoe growers, we investigated the kinetics and metabolic health effects of oral GABA and its presence in tomatoes and potatoes.

Activities and results:

Certain tomatoes and potatoes contain GABA, but the variability of GABA content across species was not systemically investigated. In addition, the effect of different food processing methods (boiling, frying, etc) on GABA content was not known. Hence this project explored GABA content in a wide range of tomatoes and potatoes, showing considerable variation in GABA content. In addition, the absorption kinetics of GABA were studied by using a pharmacokinetic approach, by comparing post-prandial GABA plasma concentrations after administration of a GABA supplement versus tomatoe juice with the same GABA dose. This study showed that orally administered GABA is absorbed and leads to a temporary increase in plasma GABA concentrations, which returns to baseline concentrations within hours. There was no difference in pharmacokinetic parameters (such as Cmax, tmax or AUC) between the tomatoe and supplement groups, indicating that GABA from a tomatoe matrix has comparable absorption as from a supplement. Finally, a randomized, double-blind, placebo-controlled intervention study was performed to investigate the effects of 3-month GABA supplementation on metabolic health in adults with prediabetes. No beneficial effects of GABA supplementation was observed on various indicators of metabolic health, such as glucose response after a oral glucose tolerance test, insulin or glucagon concentrations, or HbA1c. Interestingly, even after using GABA supplements for 3 months, GABA concentrations did not significantly increase compared to baseline, suggesting that GABA is rapidly cleared from the circulation and does not accumulate in the plasma after repeated administration. However, it was observed that fasting GABA concentrations are quite stable within a subject over different test days, but were different between individuals, suggesting inter-individual differences in mechanisms that determine GABA concentrations in the circulation. For the purpose of this project, a new liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) based method was optimized and validated to quantitatively determine GABA and glutamate concentrations in human blood. All in all, this project demonstrated that GABA is present in a wide variety of potatoes and tomatoes, and that GABA is orally bioavailable from a food matrix and supplement. Despite being orally bioavailable, using GABA supplements for 3 months did not improve metabolic health in prediabetics. Further research could focus on the mechanisms via which GABA influences glucose metabolism, and could focus on different target populations.