Acetaldehyde clearance

The mitochondrial enzyme that turns acetaldehyde into harmless acetate. When it works, the poison passes through. Roughly a third of people of East Asian descent carry a variant that works poorly - that is the flush.

Antioxidant defense increases it.

Verbatim (doi 10.1093/alcalc/agt063, Ushida & Talalay, Alcohol and Alcoholism 2013;48:526-534, Johns Hopkins): 'Sulforaphane [SF] derived from its glucosinolate precursor contained in cruciferous vegetables and related INDUCERS of the KEAP1/NRF2/ARE pathway were assessed for their potencies to induce ALDH in murine hepatoma Hepa1c1c7 cells... Potencies of these agents as inducers parallel their activities in inducing NQO1, and ARE also dependent on NRF2.' The dose-response for ALDH induction tracks the canonical Nrf2 target NQO1 and is Nrf2-dependent, which is a mechanistic test rather than a correlation. In vivo: 'SF (5 or 20 umol/day) was fed to CD-1 mice for 7 days prior to a single administration of ethanol' and 'sulforaphane feeding reduced blood acetaldehyde levels by 30%', with half-lives differing significantly between treated and untreated mice. Murine only - Hepa1c1c7 hepatoma cells and CD-1 mice. NO human acetaldehyde data. The authors' own verb is 'SF and other edible phytochemicals may ameliorate the alcohol intolerance of individuals who are polymorphic with respect to ALDH'. And a conflict in the same formula: Pueraria lobata root is a potent ALDH2 inhibitor (daidzin IC50 80 nM) that raises acetaldehyde. Two ingredients, one enzyme, opposite directions. doi 10.1093/alcalc/agt063

Ethanol-metabolizing enzyme reduces it.

The self-reinforcing loop, completed. German metabolite study (doi 10.1007/s15006-023-2860-9): 'Der THEOPHYLLIN-ANTEIL war sowohl bei FIBROSE als auch bei HOHEM FLI SIGNIFIKANT ERHÖHT, was eine ERHÖHTE CYP2E1-AKTIVITÄT WIDERSPIEGELN KÖNNTE — EIN ZEICHEN FÜR die VERSCHLIMMERUNG DER NAFLD' — raised CYP2E1 activity marks worse disease, measured in humans. And PMID 17484288 in an alcohol model: 'Ethanol administration resulted in adaptive induction of the activities of cytochrome P450... and reduction in... Glutathione-S-transferase, a phase II enzyme.' The phase-II enzyme measured was GST, not ALDH2 specifically. This edge asserts that CYP2E1 induction suppresses the phase-II arm that ALDH2 belongs to; no ALDH2-specific measurement has been reported, so this step is an inference. doi 10.1007/s15006-023-2860-9 · PMID 17484288

It reduces Acetaldehyde load.

Verbatim (pmc8742892): 'In order to reduce toxicity, acetaldehyde is rapidly further oxidized to acetate by enzyme ALDH2 inside mitochondria.' and the same reaction carries a cost: 'This reaction generates acetate and even more NADH ... As a result, the cellular NAD+/NADH ratio decreases, having a strong impact on the inhibition of fatty acid beta-oxidation, causing triacylglycerols to accumulate inside hepatocytes.' Clearing the poison still tilts the redox state toward storing fat.

It reduces Tissue scarring.

A knockout counterfactual, not an association. Verbatim (PMC6050510): 'ALDH2 deficiency accentuated CCl4-induced liver fibrosis in mice, accompanied by increased expression of collagen 1alpha1, alpha-SMA and TIMP-1. Moreover, ALDH2 knockout triggered more ROS generation, hepatocyte apoptosis and impaired mitophagy after CCl4 treatment. In cultured HSC-T6 cells, ALDH2 knockdown by transfecting with lentivirus vector increased ROS generation and alpha-SMA expression in an in vitro hepatocyte fibrosis model using TGF-beta1.' Two independent loss-of-function tests - whole-animal knockout and cell-line knockdown - both worsening fibrosis. the model is carbon tetrachloride, not alcohol; the pathway is validated, the alcohol route to it is inferred from the shared acetaldehyde chemistry and is not claimed here. PMC6050510

Event Horizon (Post-Ethanol Restoration) →

Fatty Liver Antidote (Hepatic Steatosis Reversal) →