Supplementation with γ-aminobutyric acid does not improve glucose control in patients with prediabetes

1. In this randomized controlled trial, long-term γ-aminobutyric acid (GABA) supplementation did not change postprandial glucose response or markers of glycemic control and cardiovascular health in prediabetic individuals.

2. Furthermore, long-term GABA supplementation did not lead to the accumulation of GABA in the blood.

Evidence Rating Level: 1 (Excellent)

Patients at risk for diabetes (prediabetic patients) have impaired glucose regulation and often have elevated postprandial glucose. γ-aminobutyric acid (GABA) is a neurotransmitter produced in the body that can also be consumed from dietary sources such as tomatoes, melons, and fermented foods. Animal models have suggested a potential benefit of oral GABA supplementation on blood glucose control, but this effect has not been well studied in humans. This study evaluated whether long-term oral GABA supplementation can improve glucose control in prediabetic individuals.

This randomized controlled trial included 52 individuals aged 50-70 from the Netherlands. Participants were included if they had prediabetes and a body mass index (BMI) ≥25 kg/m2. Individuals were excluded if they had known diabetes, liver, pancreatic, cardiovascular, gastrointestinal, or endocrine diseases, used medications or supplements that could impact the results, had sensitivity to local skin adhesives, experienced >5kg weight change in the prior 12 weeks, or engaged in excessive alcohol consumption, defined as >21 glasses/week for males or >14 glasses/week for females. Participants were randomized to receive either 500mg of GABA three times daily or placebo capsules for 95 days. The primary outcome measured was glucose response after an oral glucose tolerance test (OGTT). Secondary outcome measures were markers of glycemic control (glycated hemoglobin), cardiovascular health (blood pressure, circulating triglycerides, cholesterol), and sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI).

The results demonstrated that GABA supplementation did not change postprandial glucose response, markers of glycemic control, or markers of cardiovascular health compared to controls. However, participants randomized to GABA supplementation had self-reported improvements in sleep quality, but the results were non-significant after correcting for the false discovery rate. Lastly, GABA levels in the plasma were not elevated even after 95 days of supplementation. However, this study was limited by most participants having relatively early or mild stages of prediabetes, which may have obscured the possible effects of GABA on glucose control. Therefore, further studies evaluating the effects of GABA on diabetic individuals may be warranted.

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Click to read the study in The American Journal of Clinical Nutrition

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