The rates of binge drinking keep rising in the West and such activities are strongly and inversely correlated with overall quality of life. Thus, it seems that life continues to deteriorate in the West, despite what the media and doctors are telling us. Peat wrote that the negative effects of alcohol on the liver are not due to the alcohol (ethanol) per se, but due to alcohol increasing intestinal permeability, which increases endotoxin/LPS absorption into the bloodstream, which in turns harms the liver when endotoxin is transported there for detoxification. Substances that increase NAD+ and the metabolic rate have been shown to restore the gut barrier function and largely prevent the negative effects of alcohol on the liver. However, the prevention is not complete, which suggests that there are other mechanism involved in alcohol-induced liver damage. The study below demonstrated that alcohol itself increases the release of glutamic acid. The latter has known excitotoxic effects and has already been confirmed as a potent neurotoxin involved in many psychiatric and neurological conditions. It looks like the toxicity is not limited to the brain, but manifests in the liver as well, leading the researchers to label glutamic acid as a “hepatotransmitter” (a word play on its already known as a neurotransmitter). Interestingly, one of the main toxicity pathways induced by glutamate was increased nitric oxide (NO) production – a signalling molecule Ray also wrote about extensively. As such, glutamate antagonists may be able to blunt/negate this pathway and thus further limit the damage from drinking alcohol. Magnesium and taurine are some of the better known NMDA (glutamate) antagonists and unsurprisingly, both of them have shown protective effects in studies with binge drinking. Since magnesium can often cause GI irritation when used orally, that leaves taurine as the more appropriate supplement to try, and it is already known to synergize with niacinamide (which raises NAD+ and seals the gut barrier). (Non)coincidentally, both taurine and niacinamide reduce NO production, which undoubtedly contributes to their benefit seen in liver conditions.
https://www.nature.com/articles/s41467-025-60820-3
https://www.koreabiomed.com/news/articleView.html?idxno=28267
“…Korea Advanced Institute of Science and Technology (KAIST) announced on Thursday that its research team, led by Professor Jeong Won-il of the KAIST Graduate School of Biomedical Science and Engineering in collaboration with Professor Kim Won of SMG-SNU Boramae Medical Center, has identified the process of liver damage and inflammation caused by drinking alcohol at the molecular level. The team identified a new pathway in which a signaling substance called “glutamic acid” is secreted by hepatocytes when drinking alcohol, and this substance stimulates Kupffer cells, immune cells in the liver, leading to reactive oxygen species (ROS) production, inflammation, and hepatocyte death.”
“…Previously, an indirect pathway was thought to be the main culprit, with Lipopolysaccharide (LPS) from the gut stimulating Kupffer cells to induce inflammation. However, this study overturns that theory by demonstrating that hepatocytes themselves can actively stimulate immune cells. In an animal model, the team found that chronic drinking increases the expression of a glutamate transporter (VGLUT3) in hepatocytes, leading to the accumulation of glutamate, which is then released in response to changes in calcium concentration during binge drinking. This glutamic acid stimulates the mGluR5 receptor on Kupffer cells, which activates nitric oxide synthase (NOS2), leading to an inflammatory response and liver cell damage. The discovery shows that glutamic acid can also act as a hepatotransmitter in the liver. The researchers confirmed that the relevant pathways for glutamic acid synthesis (ALDH4A1), storage (VGLUT3), secretion (SNARE complex), uptake (mGluR5), and reuptake (EAAT2) are indeed operational in liver tissue. They also demonstrated that genetic or pharmacological inhibition of VGLUT3, mGluR5, and NOX2 significantly reduced liver damage and inflammation.”
