Nattokinase vs Pregnenolone

Mechanism

Nattokinase is a fibrinolytic serine protease extracted from natto (fermented soybeans). It directly degrades fibrin (the structural protein of blood clots) through four mechanisms: direct fibrinolysis, enhancement of endogenous tPA (tissue plasminogen activator) production, conversion of prourokinase to urokinase, and degradation of PAI-1 (plasminogen activator inhibitor-1). It also reduces blood viscosity and may inhibit ACE (angiotensin-converting enzyme), providing mild antihypertensive effects.

Standard Dosing

2000-4000 FU (fibrinolytic units) daily, equivalent to 100-200mg

Timing

On empty stomach, between meals or before bed. Morning and evening split dosing for 24-hour fibrinolytic coverage.

Cycle Duration

ongoing

Side Effects

• Easy bruising
• Nosebleeds
• GI upset
• Rare: serious bleeding events

Contraindications

• Active bleeding or bleeding disorders
• Scheduled surgery (discontinue 2+ weeks prior)
• Concurrent anticoagulant/antiplatelet therapy
• Hemorrhagic stroke history
• Soy allergy
• Active bleeding
• Bleeding disorders
• Pre-surgery (stop 2 weeks prior)
• Concurrent anticoagulation therapy without physician supervision

Best Stacking Partners

Mechanism

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.

Standard Dosing

Research indicates 10-50 mg daily orally for neurosteroid and cognitive support. Clinical trials in schizophrenia used up to 500 mg/day.

Timing

Morning dosing preferred (aligns with diurnal cortisol rhythm). Sublingual may provide faster onset and better bioavailability. Take with or without food.

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.

Side Effects

• Headache
• Irritability/mood changes
• Insomnia
• Acne (via androgenic metabolites)
• Heart palpitations
• Hair loss (if converting heavily down androgen pathway)
• Overstimulation
• Overstimulation and anxiety (from GABA-A antagonism at higher doses)
• Insomnia (if taken late in the day)
• Acne (from downstream androgen conversion)
• Irritability
• Hair growth or loss (from downstream hormonal changes)

Contraindications

• Hormone-sensitive cancers
• Seizure disorders (complex GABA modulation)
• Pregnancy
• PCOS
• Concurrent HRT without monitoring
• Use only with lab-guided supervision
• Hormone-sensitive cancers (breast, prostate, ovarian — due to downstream conversion)
• History of seizures (pregnenolone sulfate is pro-excitatory)
• Pregnancy and breastfeeding
• Bipolar disorder (may exacerbate manic episodes)

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