Berberine

Berberine is the most underrated supplement on this list: a plant alkaloid found in barberry, goldenseal, and Oregon grape that activates AMPK — the same cellular energy sensor targeted by metformin, the most-studied longevity drug. Meta-analyses find berberine reduces fasting blood glucose by approximately 20%, comparable to metformin, with an HbA1c reduction of 0.9% in pre-diabetic and diabetic populations. For metabolic health and insulin sensitivity, the evidence is strong (Examine.com grade A for blood glucose reduction). The surprise: berberine also shows evidence for lipid lowering (LDL reduction of 20-30% in RCTs) and gut microbiome improvement. Dose: 500mg three times daily with meals. Significant drug interactions — do not combine with cyclosporine or blood thinners without physician review.