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Pregnenolone is a hormone produced in our bodies from cholesterol. It is a precursor to DHEA and progesterone. Pregnenolone has been linked to stress and fatigue reduction. Pregnenolone has also been found to inhibit GABA receptors, thus increasing mental alertness. Pregnenolone is also thought to stimulate NMDA (N-methyl-D-aspartate) receptors which play a part in memory and learning by regulating synapses.
Pregnenolone is a hormone precursor that the body normally manufactures from cholesterol. Called the "mother hormone", pregnenolone converts into other hormones including DHEA, estrogen, testosterone, and progesterone. As with DHEA, pregnenolone levels decline with age. When maintained or restored to youthful levels, pregnenolone helps maintain proper memory and immune functions.
Pregnenolone is a steroid naturally found in animal tissues, especially in the gonads, adrenal gland and brain. Pregnenolone is synthesized from cholesterol and is a precursor for the biosynthesis of steroid hormones. In the adrenal gland, pregnenolone is a precursor to the mineralocorticoid aldosterone, the glucocorticoid cortisol, as well as dehydroepiandrosterone (DHEA) and progesterone. In the ovary, pregnenolone is a precursor to estrogens and progesterone, and, in the testis, pregnenolone is a precursor to testosterone.
Pregnenolone and its metabolite pregnenolone sulfate are now known to be synthesized in the brain either de novo from cholesterol or from other metabolites. Pregnenolone and pregnenolone sulfate found in the brain and central nervous system are referred to as neurosteroids.
BENEFIT OF PREGNENOLONE:
Pregnenolone - enhances the ability to acquire knowledge and motivation.
Pregnenolone - reduce high stress induced fatigue.
Pregnenolone is known chemically as 3-Hydroxypregn-5-en-20-one; delta 5-pregnen-3 beta-ol-20-one, and 17 beta-(1-ketoethyl)-delta 5-androstene-3 beta-ol. Its abbreviation is PREG and the abbreviation of its metabolite, progesterone sulfate, is PREG S. Pregnenolone is a lipophilic solid substance that is sparingly soluble in water. Pregnenolone has the following chemical structure:
MECHANISM OF ACTION
Memory enhancement has been observed in aged animals when given pregnenolone or pregnenolone sulfate. Pregnenolone sulfate is both a gamma-aminobutyrate (GABA) antagonist and a positive allosteric modulator at the N-methyl-D-asparatate (NMDA) receptor and may reinforce neurotransmitter systems that may decline with age.
Pregnenolone sulfate was found to stimulate acetylcholine release in the adult rat hippocampus. Acetylcholine release may be due to pregnenolone sulfate's negative modulation of the GABA (A) receptor complex and positive modulation of the NMDA receptor. While a modest increase in acetylcholine release facilities memory processes, elevation of acetylcholine beyond an optimal level is ineffective in doing so.
Little is known about the pharmacokinetics (PK) of pregnenolone in humans. Some PK studies have been done in animals. The absorption of pregnenolone, similar to the absorption of most steroids, is variable. It appears that some pregnenolone is absorbed from the small intestine and distributed throughout the body. How much is taken up by the liver and metabolized is unclear. Likewise, it is unclear how much of an ingested pregnenolone dose is taken up by the brain. Metabolites of injected pregnenolone in the rat brain include pregnenolone sulfate, progesterone, 5 alpha-pregnane-3, 20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one or allopregnanolone and DHEA. In other tissues, pregnenolone may be metabolized to DHEA, testosterone, estrogens, cortisol and aldosterone.
INDICATIONS AND USAGE
Pregnenolone may have some efficacy as a memory enhancer; this has so far been demonstrated in various animal models but not yet in humans. There are unsubstantiated claims that pregnenolone is useful in Alzheimer's disease, some forms of cancer and arthritis, in degenerative diseases associated with aging in general and in obesity.
There are several studies showing a correlation between deficiencies in cognitive performance in aged animals and low pregnenolone levels in the brains of these animals, especially in the hippocampus. Performance or memory tests have been shown to improve in these animals when hippocampal pregnenolone levels were increased via intraperitoneal or bilateral intrahippocampal injection of pregnenolone sulfate.
There is direct evidence from many of these studies that pregnenolone sulfate stimulates release of acetylcholine in the hippocampus. There is additional evidence that suggests that exogenous pregnenolone can reinforce neurotransmitter systems that normally decline with age. A "global stimulatory effect on central cholinergic neurotransmission" has been suggested by one research group.
Though significant favorable results have been obtained with respect to memory enhancement in aged animals, human studies have yet to commence. These are warranted. Meanwhile, claims that supplemental pregnenolone is helpful in Alzheimer's disease are unsubstantiated. And there is no credible evidence that pregnenolone is useful in the treatment of arthritis, cancer, degenerative diseases or obesity.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
Pregnenolone is contraindicated in those with prostate, breast and uterine cancer.
Pregnenolone should be avoided by children, pregnant women and nursing mothers.
Because of the theoretical possibility that pregnenolone may lower seizure threshold—pregnenolone sulfate negatively modulates GABA (A) receptors in animals—those with seizure disorders should avoid pregnenolone.
To date there are no reported significant adverse effects. Mild gastrointestinal effects, such as nausea, have been noted. However, pregnenolone may be converted to steroids such as DHEA, and DHEA does cause various adverse effects such as acne and hair loss, especially in women.
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