Ashwagandha (KSM-66) — Adaptogen / Ayurvedic botanical
Ashwagandha's primary bioactive compounds are withanolides (especially withaferin A and withanolide D), alkaloids, and saponins. Mechanisms: (1) HPA axis modulation — reduces cortisol output via adrenal modulation; (2) GABA-A receptor modulation (triethylene glycol fraction) — anxiolytic; (3) testosterone/LH elevation in stressed/hypogonadal men via HPG axis normalization; (4) anti-inflammatory via NF-κB and COX-2 suppression; (5) thyroid stimulation (mild T4 elevation). KSM-66 is a full-spectrum root extract standardized to ≥5% withanolides with 22 clinical trials supporting it.
Overview
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Compound Class
Adaptogen / Ayurvedic botanical
Mechanism of Action
Ashwagandha's primary bioactive compounds are withanolides (especially withaferin A and withanolide D), alkaloids, and saponins. Mechanisms: (1) HPA axis modulation — reduces cortisol output via adrenal modulation; (2) GABA-A receptor modulation (triethylene glycol fraction) — anxiolytic; (3) testosterone/LH elevation in stressed/hypogonadal men via HPG axis normalization; (4) anti-inflammatory via NF-κB and COX-2 suppression; (5) thyroid stimulation (mild T4 elevation). KSM-66 is a full-spectrum root extract standardized to ≥5% withanolides with 22 clinical trials supporting it.
Regulatory Status
OTC dietary supplement. GRAS status. Not FDA-approved for any indication.
Evidence Level
Moderate — 22+ clinical trials for KSM-66 specifically. Multiple RCTs demonstrate stress reduction, cortisol lowering, and testosterone improvement. USPSTF has not reviewed. No formal guideline recommendations.