Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Ashwagandha (KSM-66) | Reishi Mushroom (Ganoderma lucidum) | |
|---|---|---|
| Category | Adaptogens | Adaptogens |
| Standard Dose | 600mg KSM-66 daily (300mg 2x/day) | 1000-3000mg daily (dual extract: hot water + alcohol for both polysaccharides and triterpenes) |
| Timing | Morning and evening with meals. Evening dose supports sleep quality via cortisol reduction. | Evening preferred (calming, supports sleep). With meals. |
| Cycle Duration | Cycle 8-12 weeks on, 2-4 weeks off (to prevent adaptogenic tolerance) | ongoing or cycle 12 weeks on, 4 weeks off |
| 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)
Reishi contains triterpenoids (ganoderic acids, >130 identified) and polysaccharides (beta-glucans). Ganoderic acids inhibit histamine release, 5-alpha-reductase (DHT reduction), and ACE (angiotensin-converting enzyme). Beta-glucans (1,3/1,6-D-glucan) activate innate immunity via Dectin-1, CR3, and TLR-2 receptors on macrophages, dendritic cells, and NK cells. Reishi modulates the adaptive immune system by promoting Th1/Th2 balance and enhancing regulatory T-cell function. It also supports GABAergic signaling (calming effect), inhibits NF-kB, and modulates gut microbiome composition. Triterpenes support liver function via Phase I/II enzyme modulation.
1000-3000mg daily (dual extract: hot water + alcohol for both polysaccharides and triterpenes)
Evening preferred (calming, supports sleep). With meals.
ongoing or cycle 12 weeks on, 4 weeks off
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