Ashwagandha (KSM-66) vs Maca Root (Gelatinized)

Mechanism

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.

Standard Dosing

600mg KSM-66 daily (300mg 2x/day)

Timing

Morning and evening with meals. Evening dose supports sleep quality via cortisol reduction.

Cycle Duration

Cycle 8-12 weeks on, 2-4 weeks off (to prevent adaptogenic tolerance)

Side Effects

• Drowsiness
• GI upset
• Thyroid hormone elevation
• Rare: liver injury (case reports, mainly with combination products)
• Vivid dreams
• Increased appetite

Contraindications

• Hyperthyroidism or Graves' disease
• Autoimmune conditions (immunostimulatory)
• Pregnancy (traditionally considered emmenagogue/abortifacient)
• Nightshade sensitivity (Solanaceae family)

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Mechanism

Maca (Lepidium meyenii) contains unique macamides and macaenes (fatty acid derivatives), glucosinolates, and alkaloids. Unlike most adaptogens, maca does not directly affect testosterone, estrogen, or cortisol levels in blood. Instead, it appears to work as a 'hormonal normalizer' by acting on the hypothalamic-pituitary axis, modulating GnRH pulsatility and improving receptor sensitivity. Macamides interact with the endocannabinoid system (FAAH inhibition) and may modulate GABA and opioid pathways. Maca improves sexual function and desire through mechanisms independent of direct hormone elevation — likely central nervous system pathways.

Standard Dosing

1500-3000mg gelatinized maca daily

Timing

Morning with breakfast. Can be added to smoothies.

Cycle Duration

Cycle 12 weeks on, 4 weeks off, or ongoing

Side Effects

• GI upset/bloating (raw maca — gelatinized is much better tolerated)
• Insomnia
• Mood changes
• Increased heart rate (rare)
• Hormonal acne (rare)

Contraindications

• Hormone-sensitive cancers (glucosinolate metabolites may have hormonal effects)
• Severe hypothyroidism (goitrogenic potential)

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