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Patients with Fitzpatrick IV-VI skin should be monitored for potential irritation during initial use, particularly in combination with other actives, and formulations should be pH-controlled (pH 3.5 or lower for efficacy without excessive irritation)

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It is also possible that the antioxidants administered are inaccessible to the source of free radicals, particularly if ROS are generated in intracellular organelles and compartments.[9] Furthermore, antioxidants do not inhibit ROS production and antioxidant vitamins do not scavenge H2O2, which may be more important than •O2 − in cardiovascular diseases.[9] Regarding cohorts included in large trials, most subjects had significant cardiovascular disease, in which case damaging effects of oxidative stress might be irreversible