Alpha Lipoic Acid (ALA) vs Pregnenolone

Mechanism

ALA is a dithiol compound that functions as a cofactor for mitochondrial alpha-keto acid dehydrogenases (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase). Both ALA and its reduced form DHLA are potent antioxidants capable of regenerating other antioxidants including vitamin C, vitamin E, and glutathione. ALA activates AMPK, improving glucose uptake via GLUT4 translocation, and modulates NF-kB-mediated inflammatory signaling. It chelates redox-active metals (Fe2+, Cu2+).

Standard Dosing

300-600mg R-ALA daily

Timing

On empty stomach, 30-60 min before meals. Split doses for higher amounts.

Cycle Duration

ongoing or cycle 12 weeks on, 4 weeks off

Side Effects

• GI upset/nausea
• Skin rash
• Hypoglycemia symptoms
• Body odor changes

Contraindications

• Thiamine (B1) deficiency (ALA increases thiamine demand)
• Hypoglycemia-prone individuals without monitoring
• Autoimmune thyroid conditions (monitor thyroid function)

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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