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Pregnancy and breastfeeding : do not start glutathione or NAC supplements without medical advice, as evidence for routine supplementation in these groups is limited (despite medicinal use of NAC for paracetamol overdose under specialist supervision)

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Target-driven exit rules: transition the clinical mindset from treating for a trial period to exiting upon target achievement. For instance, a 36 months metabolic optimization window should be pre-set to achieve a clinically meaningful weight-loss threshold and improve IR markers

In addition, downregulation of Notch signaling promotes ferroptosis in LEC by impairing the Nrf2/GPX4 antioxidant pathway, which contributes to the development of cataracts