Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Ashwagandha (KSM-66) | Gotu Kola (Centella asiatica) | |
|---|---|---|
| Category | Adaptogens | Nootropics |
| Standard Dose | 600mg KSM-66 daily (300mg 2x/day) | 500-1000 mg/day of standardized extract (35-45% triterpenes) or 750-1500 mg/day of whole herb extract |
| Timing | Morning and evening with meals. Evening dose supports sleep quality via cortisol reduction. | Morning or split morning/afternoon. With or without food. Acute mood effects (alertness, reduced anger) noted within 1 hour of dosing. |
| Cycle Duration | Cycle 8-12 weeks on, 2-4 weeks off (to prevent adaptogenic tolerance) | Ongoing; traditional use suggests no cycling required. Clinical trials run 2-6 months. |
| Evidence Level | strong_human | moderate_human |
Ashwagandha's primary bioactives are withanolides (particularly withaferin A and withanolide D). KSM-66 is a full-spectrum root extract standardized to >5% withanolides. It modulates the HPA axis by reducing cortisol output (20-30% reduction in trials), likely through GABAergic activity (withanolides are GABA-mimetic at GABA-A receptors) and by normalizing cortisol receptor (GR) sensitivity. It also inhibits the NMDA-induced neurotoxicity pathway, enhances DHEA-S production, promotes thyroid function (increases T4 to T3 conversion), upregulates antioxidant enzymes (SOD, catalase, glutathione peroxidase), and has demonstrated sirtuin-activating properties.
600mg KSM-66 daily (300mg 2x/day)
Morning and evening with meals. Evening dose supports sleep quality via cortisol reduction.
Cycle 8-12 weeks on, 2-4 weeks off (to prevent adaptogenic tolerance)
Pentacyclic triterpenes — asiaticoside, madecassoside, asiatic acid, and madecassic acid — provide neuroprotection through multiple mechanisms: inhibition of acetylcholinesterase activity and enhancement of cholinergic transmission; reduction of phospholipase A2 (PLA2) activity to attenuate neuroinflammation; protection against beta-amyloid aggregation and tau hyperphosphorylation; and upregulation of BDNF to promote neuronal growth and synaptic plasticity. Asiaticoside enhances collagen synthesis and wound healing, while asiatic acid activates the MAPK/ERK pathway to promote neurite outgrowth.
500-1000 mg/day of standardized extract (35-45% triterpenes) or 750-1500 mg/day of whole herb extract
Morning or split morning/afternoon. With or without food. Acute mood effects (alertness, reduced anger) noted within 1 hour of dosing.
Ongoing; traditional use suggests no cycling required. Clinical trials run 2-6 months.
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