Ashwagandha (KSM-66) — The Adaptogen
Ashwagandha (Withania somnifera) is an Ayurvedic adaptogen with the most robust clinical evidence base of any herbal supplement. KSM-66 (full-spectrum root extract) has demonstrated effects on cortisol, testosterone, thyroid function, cognitive performance, and physical endurance in multiple RCTs.
Mechanism of Action
Withanolides (the active steroidal lactones) modulate the HPA axis, reducing cortisol secretion. They also inhibit NF-κB and COX-2 (anti-inflammatory), activate GABA-A receptors (anxiolytic), and may stimulate thyroid hormone synthesis. Ashwagandha also increases DHEA-S and testosterone via LH stimulation.
Human Trial Evidence
A 2012 Indian Journal of Psychological Medicine RCT (Chandrasekhar et al.) showed 300 mg KSM-66 twice daily reduced serum cortisol by 27.9% and anxiety scores by 56% over 60 days. Multiple RCTs confirm: improved VO2 max (+7%), increased testosterone (+15–17%), improved sleep quality, and enhanced cognitive function.
Dosing Protocol
300–600 mg/day KSM-66 or Sensoril extract. Best taken with food. Evening dosing preferred for sleep benefits. Cycle 8–12 weeks on, 2–4 weeks off. Avoid in thyroid disorders (may stimulate thyroid).
Safety & Contraindications
Well-tolerated in trials up to 1,250 mg/day. Rare: GI upset, drowsiness. Case reports of liver injury at very high doses (>1,500 mg/day) — use standardized extracts at recommended doses. Avoid in pregnancy (uterotonic), autoimmune disease (immunostimulant), and thyroid disorders.