Collagen (Type I, II, III) vs Pregnenolone

Mechanism

Hydrolyzed collagen peptides are absorbed as di- and tripeptides (primarily hydroxyproline-proline and hydroxyproline-glycine) via PepT1 transporters in the small intestine. These bioactive peptides accumulate in skin, cartilage, and bone where they stimulate fibroblast proliferation and extracellular matrix synthesis by upregulating collagen gene expression (COL1A1, COL3A1). They also inhibit MMP (matrix metalloproteinase) activity that degrades existing collagen, and stimulate hyaluronic acid production by dermal fibroblasts.

Standard Dosing

10-20g hydrolyzed collagen peptides daily

Timing

Any time; often added to morning coffee or post-workout shake. For joint support, take with vitamin C 30-60 min before exercise. Type II collagen (undenatured, UC-II) taken on empty stomach.

Cycle Duration

ongoing (minimum 8-12 weeks for visible results)

Side Effects

• Mild bloating
• GI discomfort
• Unpleasant taste
• Rare: calcium elevation (if calcium-containing marine source)
• Feeling of fullness

Contraindications

• Fish/shellfish allergy (if marine-sourced)
• Phenylketonuria (collagen contains phenylalanine)
• Histamine intolerance (bone broth collagen may be high in histamine)

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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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