Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Ashwagandha (KSM-66) | Celastrus Paniculatus | |
|---|---|---|
| Category | Adaptogens | Nootropics |
| Standard Dose | 600mg KSM-66 daily (300mg 2x/day) | 500-1000 mg/day of seed extract (standardized to >8% polyphenols) or 10-15 seeds daily (traditional Ayurvedic dosing, escalated from 1 seed/day) |
| Timing | Morning and evening with meals. Evening dose supports sleep quality via cortisol reduction. | Morning, with or without food. Traditional practice involves gradual dose escalation starting from 1 seed daily, increasing by 1 seed per day up to 10-15. |
| Cycle Duration | Cycle 8-12 weeks on, 2-4 weeks off (to prevent adaptogenic tolerance) | Traditionally used in 30-60 day courses. No established cycling protocol from clinical data. |
| Evidence Level | strong_human | animal_plus_anecdotal |
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)
Seed oil contains sesquiterpenes, alkaloids (celastrine, paniculatin), and polyunsaturated fatty acids that demonstrate dose-dependent cholinergic activity by inhibiting acetylcholinesterase (AChE) and increasing acetylcholine levels in hippocampal and cortical regions. Provides neuroprotection against oxidative stress through elevation of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Seed extracts attenuate hydrogen peroxide- and glutamate-induced excitotoxic injury in neuronal cells, and exhibit anti-inflammatory and anxiolytic properties.
500-1000 mg/day of seed extract (standardized to >8% polyphenols) or 10-15 seeds daily (traditional Ayurvedic dosing, escalated from 1 seed/day)
Morning, with or without food. Traditional practice involves gradual dose escalation starting from 1 seed daily, increasing by 1 seed per day up to 10-15.
Traditionally used in 30-60 day courses. No established cycling protocol from clinical data.
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