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But chronic high-dose use may: Overstimulate metabolic pathways Alter methylation balance (since NNMT is tied to methyl donor cycling) Lead to unintended side effects like fatigue, irritability, or hormonal imbalance Stick to researched dosing windows (typically 1020 mg/day for short cycles in animal models) 2

295 This indicates that Trx acts as an upstream inhibitor of ASK1, and Trx/ASK1 signalling is an upstream modulator of p38MAPK

J Nutr Sci