Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Pregnenolone | Sulforaphane (Broccoli Seed Extract) | |
|---|---|---|
| Category | Supplements | Supplements |
| Standard Dose | Research indicates 10-50 mg daily orally for neurosteroid and cognitive support. Clinical trials in schizophrenia used up to 500 mg/day. | 10-30mg sulforaphane daily (equivalent to ~100-200mg broccoli seed extract standardized to glucoraphanin + myrosinase) |
| Timing | Morning dosing preferred (aligns with diurnal cortisol rhythm). Sublingual may provide faster onset and better bioavailability. Take with or without food. | On empty stomach or with light meal. Myrosinase enzyme required for conversion from glucoraphanin — ensure supplement contains it or add mustard seed powder. |
| Cycle Duration | Ongoing with periodic reassessment. Cycle 5 days on / 2 days off, or 3-4 weeks on / 1 week off to prevent downstream hormone accumulation. | ongoing |
| Evidence Level | moderate_human | strong_human |
Pregnenolone is the 'master steroid' synthesized from cholesterol via CYP11A1 (side-chain cleavage enzyme) in adrenal glands, gonads, and brain. It serves as the biosynthetic precursor to all steroid hormones (progesterone, DHEA, cortisol, testosterone, estradiol, aldosterone). In the CNS, pregnenolone and its sulfated derivative (pregnenolone sulfate) function as potent neurosteroids: pregnenolone sulfate is a positive allosteric modulator of NMDA receptors enhancing glutamatergic neurotransmission, a negative modulator of GABA-A receptors (increasing neural excitability), and an activator of TRPM3 calcium channels. It also modulates sigma-1 receptors involved in neuroplasticity.
Research indicates 10-50 mg daily orally for neurosteroid and cognitive support. Clinical trials in schizophrenia used up to 500 mg/day.
Morning dosing preferred (aligns with diurnal cortisol rhythm). Sublingual may provide faster onset and better bioavailability. Take with or without food.
Ongoing with periodic reassessment. Cycle 5 days on / 2 days off, or 3-4 weeks on / 1 week off to prevent downstream hormone accumulation.
Sulforaphane is the most potent natural activator of the Nrf2-ARE (antioxidant response element) pathway. It modifies Keap1 cysteine residues, releasing Nrf2 to translocate to the nucleus and upregulate >200 cytoprotective genes including NQO1, glutathione S-transferases, heme oxygenase-1, and UDP-glucuronosyltransferases (Phase II detox enzymes). It also inhibits HDAC activity (epigenetic modification), induces Phase II/III xenobiotic metabolism, and suppresses NF-kB inflammatory signaling.
10-30mg sulforaphane daily (equivalent to ~100-200mg broccoli seed extract standardized to glucoraphanin + myrosinase)
On empty stomach or with light meal. Myrosinase enzyme required for conversion from glucoraphanin — ensure supplement contains it or add mustard seed powder.
ongoing
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