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When COMT is slow, more 4-OHE2 remains available for oxidation to reactive quinones increasing demand on GSTM1/GSTT1 glutathione conjugation at exactly the point where their absence is most consequential

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10.1016/j.tox.2016.08.016 118 Pogrmic-MajkicK.SamardzijaD.Stojkov-MimicN.VukosavljevicJ.Trninic-PjevicA.KopitovicV.et al (2018)

Some people notice gradual improvement in skin texture and quality over weeks, while others may take longer depending on condition, lifestyle, and treatment plan