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However, if one component of the redox buffer partitions selectively into the MLO, that would lead to a very different redox environment in the MLO compared to its environment

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On the other hand, lipid-soluble antioxidants as vitamin E cross the BBB slowly and may require prolonged exposure to achieve meaningful brain concentrations, where none of the vitamin-based AMS trials assessed these agents reach the relevant target tissues, this evident limitation strongly constrains interpretation of clinical outcomes and underscores the PK-PD disconnect between theoretical neuroprotective effect and observed efficacy (Table 3)

For example, one early protocol for substance use disorders employed 500-1,000 mg of NAD+ per day delivered by slow intravenous infusion over several consecutive days

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