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[1] [2] However, longstanding neurological complications, such as peripheral neuropathy or cognitive changes, may require three to six months of consistent treatment before significant improvement occurs, and some damage may be irreversible if treatment is delayed

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Advanced insulin resistance, mitochondrial damage from chronic oxidative stress, or inflammatory states can create barriers to AMPK activation and NAD+ utilization that require co-interventions (caloric restriction, anti-inflammatory compounds, or antioxidant support)