Oxidation via CYP2E1 (5-10%) - TOXIC Creates NAPQI (N-acetyl-p-benzoquinone imine)the dangerous toxic metabolite INCREASES by 80% during pregnancy NAPQI measured at 43% HIGHER in first trimester when fetal brain is most vulnerable NAPQI must be immediately neutralized by glutathione When glutathione is depleted, NAPQI causes cellular damage Crosses placenta and damages fetal brain The Perfect Storm During Pregnancy Research reveals dramatic shifts in how pregnant women metabolize acetaminophen: Safe sulfation pathway DECREASES by 33% Toxic oxidation pathway INCREASES by 80% Glutathione levels DROP by 36-87% (when you need it most) Result: 43% MORE toxic NAPQI formed in first trimester Even though glucuronidation increases, it CANNOT compensate for the massive increase in toxic metabolite production combined with dramatically reduced glutathione reserves
How Does Glutathione IV Work

AICART: aminoimidazolecarboxamide ribonucleotide transferase BHMT: betaine-homocysteine methyltransferase CBS: cystathionine -synthase CTGL: -cystathionase DHFR: dihydrofolate reductase DMGD: dimethylglycine dehydrogenase DNMT: DNA-methyltransferase FTD: 10-formyltetrahydrofolate dehydrogenase FTS: 10-formyltetrahydrofolate synthase GCS: -glutamylcysteine synthetase GDC: glycine decarboxylase (glycine cleavage system) GNMT: glycine N-methyltransferase GPX: glutathione peroxidase GR: glutathione reductase GS: glutathione synthetase MAT-I: methionine adenosyl transferase I MAT-III: methionine adenosyl transferase III MS: methionine synthase MTCH: 5,10-methenyltetrahydrofolate cyclohydrolase MTD: 5,10-methylenetetrahydrofolate dehydrogenase MTHFR: 5,10-methylenetetrahydrofolate reductase NE: non-enzymatic conversion PGT: Phosphoribosyl glycinamidetransformalase SAAH: S-adenosylhomocysteine hydrolase SDH: sarcosine dehydrogenase SHMT: serinehydroxymethyltransferase TS: thymidylate synthase Metabolites

Retrieved 13 March 2021, from Henninge J, Pepaj M, Hullstein I, Hemmersbach P
Milani A, Basirnejad M, Shahbazi S, Bolhassani A