Digestive Enzymes (Broad Spectrum) vs Pregnenolone

Mechanism

Broad-spectrum digestive enzyme complexes supplement endogenous pancreatic and brush border enzyme production. Key enzymes include: lipase (triglyceride hydrolysis to fatty acids/glycerol), protease/peptidase (protein to amino acids via peptide bond cleavage), amylase (starch to maltose/glucose), lactase (lactose to glucose/galactose), cellulase (plant fiber breakdown), and invertase (sucrose hydrolysis). They reduce osmotic load in the small intestine, decrease bacterial fermentation of undigested substrate, and improve nutrient bioavailability.

Standard Dosing

1-2 capsules with each main meal

Timing

Immediately before or at the start of each meal. Not needed for small snacks.

Cycle Duration

ongoing as needed

Side Effects

• GI cramping if taken without food
• Allergic reactions (rare)
• Mouth ulcers from chewing enzyme capsules
• Perianal irritation from lipase at very high doses

Contraindications

• Acute pancreatitis
• Known allergy to enzyme sources (porcine, fungal, fruit-derived)

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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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