Also known as: Pregn-5-en-3β-ol-20-one, P5
Pregnenolone is a steroid hormone synthesized from cholesterol and serves as the master precursor for nearly all other steroid hormones, including DHEA, progesterone, cortisol, testosterone, and estrogen. Interest in supplementation centers on age-related cognitive decline and hormonal support.
Pregnenolone is the biochemical starting point of the steroidogenic pathway, synthesized from cholesterol by the enzyme cytochrome P450scc in the mitochondria of the adrenal cortex, gonads, and brain. From pregnenolone, the body produces progesterone, DHEA, cortisol, aldosterone, testosterone, and estradiol through various enzymatic conversions. It is also a neurosteroid, meaning it is produced in the brain and modulates GABA-A, NMDA, and sigma-1 receptors, influencing mood, memory, and neuroprotection. Pregnenolone levels decline with age, similar to DHEA. Preliminary research suggests potential benefits for cognitive function, mood disorders, and schizophrenia symptoms, but large-scale clinical trials are lacking. As a prohormone with the potential to influence multiple downstream hormonal pathways, pregnenolone supplementation carries significant regulatory restrictions. In Germany and the EU, it is classified as a hormone and is not available as a dietary supplement. In the United States, it is sold over the counter but should be used only under medical guidance with hormone level monitoring.
As a neurosteroid, pregnenolone modulates NMDA receptors involved in learning and memory. Pilot studies in older adults and patients with schizophrenia have shown improvements in verbal memory and attention.
Pregnenolone's metabolite allopregnanolone is a potent positive modulator of GABA-A receptors. Clinical research suggests pregnenolone supplementation may improve depressive symptoms, though evidence is still preliminary.
Once daily in the morning
Start with the lowest effective dose. Hormone levels (pregnenolone, DHEA, cortisol, sex hormones) should be monitored regularly. Prescription-only in Germany, the EU, and many other countries.
Standardized dosing and improved absorption
Bypassing first-pass liver metabolism
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