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Saturday, September 6, 2008

Pregnenolone Helps the Brain

Some elderly people are senile while others maintain alert mental function and memory. Why the difference? Recent research indicates that pregnenolone levels are higher in those with good memory and mental function but depleted in those who are senile. Researchers pointed out, "Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the pregnenolone sulfate (PREG-S)."1 The pregnenolone works, in part, it is believed, by upregulating "acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus."1 It was concluded, "Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission."1

It is now well established that brain levels of pregnenolone decrease with age, although this decrease varies from individual to individual, with some people losing the neurotransmitter at a more alarming rate. Researchers said, "PREG S is both a γ-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-d-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age."2 This means pregnenolone exerts a powerful beneficial effect on congnition through two separate mechanisms, first by reducing GABA (GABA causes brain fog), and second by stimulating NMDA receptors, which leads to improved alertness, creativity, and memory.3
In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.3
This research holds out the intriguing possibility that pregnenolone supplementation could upregulate the major neurotransmitter involved in memory, creativity and alertness, while also boosting mood and physical and mental stamina.4

In a comprehensive and exceptional summary of the research, International Antiaging Magazine reports that pregnenolone is not limited to the two above-described methods of action. Amazingly, this wonder hormone has two additional mind boosting methods of action:
Pregnenolone also acts as sigma-1 receptor agonist, resulting in the increased release of acetylcholine, a neurotransmitter involved in memory and learning. Acetylcholine typically declines in normal aging and is severely altered in neurodegenerative diseases such as Alzheimer’s. Preg-S infused into the brains of rats was shown to augment acetylcholine release by more than 50% while improving recognition of a familiar environment. In addition, stimulation of acetylcholine release induces an increase in paradoxical, or REM, sleep, which has been shown to influence memory processes.

Besides its function as a regulator of neurotransmitter function, pregnenolone has been shown to stimulate growth of new nerve tissue (known as neurogenesis). Previously, scientists believed that brain damage was irreversible and that neural repair was impossible; but recently researchers discovered that the brain is, in fact, capable of generating new neurons — good news for those with neurodegenerative diseases and declining cognitive function. In a fascinating study, researchers demonstrated that infusion of Preg-S into the brains of both young (3 months) and old (20 months) rats stimulated neurogenesis.5 [Citations omitted. Emphasis supplied.]
Our review of these studies indicates that pregnenolone operate by five separate methods of action, all of which boost brain function and capability:
  1. It decreases GABA (a brain fog creator) thus improving alertness;
  2. It stimulates NMDA receptors, improving memory;
  3. It is a sigma-1 receptor agonist, increasing acetylcholine, a major neurotransmitter;
  4. It stimulates neurogenesis (the growth of new brain cells); and
  5. It improves parameters of REM sleep, which in turn improves mental functioning.
By all accounts this is a rather remarkable hormone, with a good safety profile and a low cost. Since pregnenolone is not well absorbed orally, the best way to take it is with sublingual 10 mg. tablets (up to 5 per day).

Statement of conflict of interest: The author of this article, Michael Christian, has no affiliation with any of the sources listed.


  1. Progress in Neurobiology; Volume 71, Issue 1, September 2003, Pages 43-48; The Role of Neuroactive Steroids in Healthy Ageing Therapeutical Perspectives. Individual differences in cognitive aging: implication of pregnenolone sulfate. Willy Mayo, Olivier Georgea, Sonia Darbrab, Jean-Jacques Bouyera, Monique Valléea, Muriel Darnaudéryc, Marc Pallarèsb, Valérie Lemaire-Mayoa, Michel Le Moala, Pier-Vincenzo Piazzaa and Nora Abrousa. doi:10.1016/j.pneurobio.2003.09.006. (Accessed 9/5/2008.)
  2. Neurosteroids: Deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Monique Vallée, Willy Mayo, Muriel Darnaudéry, Colette Corpéchot, Jacques Young, Muriel Koehl, Michel Le Moal, Etienne-Emile Baulieu, Paul Robel, and Hervé Simon. Proceedings of the The National Academy of Sciences of the USA (PNAS) December 23, 1997 vol. 94 no. 26 14865-14870. (Accessed 9/5/2008.)
  3. Pregnenolone and Mental Function. (Accessed 9/5/2008.)
  4. Ray Sahelian. Pregnenolone. Avery, 1997.
  5. Pregnenolone: A potent memory enhancer and cognitive rejuvenator.
  6. International Antiuaging Magazine. Pregnenolone — A potent memory enhancer and cognitive rejuvenator. (19 References.) (Accessed 9/5/2008.)

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