Effective Capture of Acrolein <i>In Vivo</i> Using the Combination of Ergothioneine and Aminobutyric Acid, or Mushrooms as a Carrier, in Both Mice and Human Models

Acrolein (ACR), an α,β-unsaturated aldehyde generated during metabolism, accumulates in the body and contributes to chronic disease development. This study evaluated the <i>in vivo</i> ACR-scavenging effects of ergothioneine (EGT), alone or with γ-aminobutyric acid (GABA), in mice and humans. After confirming the formation of EGT-ACR adducts (EGT-ACR-(1-4), EGT-2ACR-(1-3), and EGT-3ACR) <i>in vitro</i>, we used UHPLC-QTOF-MS/MS and UHPLC-QQQ-MS/MS to detect these adducts in urine and feces following EGT or EGT + GABA administration. Mono- and di-ACR adducts increased dose-dependently in mice, and GABA (one-fifth of the EGT dose) enhanced adduct formation by up to twofold. Human studies confirmed both the dose-response relationship of EGT's ACR scavenging and the synergistic effect of GABA whether EGT was delivered as pure capsules or via <i>Boletus edulis</i>. These findings identify EGT as a potent <i>in</i> <i>vivo</i> ACR scavenger and support its potential as a dietary strategy to mitigate ACR-related chronic disease risk.