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146,147 Special care is needed with natural and OTC compounds, as they may have unreliable safety or pharmacokinetic profiles, requiring more stringent trials before approval for a major CV indication

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In granulosa cells of women with endometriosis, elevated lipid peroxidation markers such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been observed, accompanied by decreased glutathione (GSH) and glutathione peroxidase 4 (GPx4), key inhibitors of ferroptosis ( Ferroptosis exerts a double-edged effect in endometriosis: while it damages ovarian granulosa cells, oocytes, and embryosdisrupting oocyte maturation, decreasing oocyte retrieval rates, and impairing embryonic developmentit also promotes ectopic lesion growth through downstream signaling pathways that enhance angiogenesis and inflammation ( Therapeutically, ferroptosis inducers can promote lipid ROS accumulation and endometriotic cell death but may exacerbate granulosa cell damage, while ferroptosis inhibitors protect granulosa cells against oxidative damage

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Consequently, rigorous safety evaluations including long-term metabolic monitoring, immune profiling, and cancer surveillance are imperative to delineate the therapeutic window of NAD + -boosting strategies