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In contrast, heavy metals, endocrine disrupting chemicals, cigarette smoking, and a diet low in antioxidants and fiber were, alongside genetic predispositions, associated with UFs formation

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Genetic factors such as p53 and nuclear factor erythroid 2-related factor 2 (Nrf2) also affect susceptibility by regulating the expression of solute carrier family 7 member 11 (SLC7A11) or influencing antioxidant defenses [92]

Caffeine shows significant chronic psychoactive metabolite accumulation with daily use [34], while paraxanthine and 1-MX have mostly-inactive metabolites that are rapidly excreted [35]