Brain Tonic Synergy

wo principal memory-function nutrients are pregnenolone, and choline. They are established neuroenhancers. Both have been studied scientifically for a long time, with favorable results, and both are without significant side effects. But until now - as far as we know - the complexities of the interrelationship of pregnenolone and choline have not been explored.* Thus a recent report in Brain Research is as fascinating as it is welcome.1

* Speaking of complexity - but of an unnecessary sort - the research on pregnenolone and choline comes out of INSERM, France's answer to the United States's National Institutes of Health. Despite this liability - INSERM is still recommending iron supplements for all children - some good work does appear, perhaps owing to the residency of the esteemed Professor Etienne-Emile Beaulieu, who contacted us several months ago suggesting collaboration in a study on pregnenolone. Nothing has yet come out of the relationship.

This report finds a correlation between endogenous levels of the neurosteroid pregnenolone sulfate in the hippocampus (the seat of emotions in the brain) and the cholinergic-attributed performance of aged rats in a spatial memory task. Pregnenolone and choline are allied through their activity in the hippocampus and their effects on memory. Pregnenolone, which is synthesized naturally in the brain,2 is known as a promnesic, a substance serving to increase memory retention and resurrect old memories, thus making it much the opposite of an amnesic. Choline is a nutrient precursor to acetylcholine, an important memory messenger molecule. Changes in cholinergic function are thought to represent age-related neurobiological events that underlie behavioral or cognitive impairments.3

In the Brain Research experiment, the effect of increasing doses of pregnenolone sulfate on the release of acetylcholine by the hippocampus was investigated. The researchers found a dose-dependent response: a very small amount of pregnenolone induced a short-term (20-min) enhancement of acetylcholine output, by about 120% over baseline, whereas a slightly larger amount induced a long-term (80-min) increase that peaked around 300% over baseline. Acetylcholine is strongly associated with focus, attention, and mental clarity (according to Durk Pearson, Clint Eastwood has acknowledged that using choline helped make him a better public speaker). Given that pregnenolone has been independently associated with improved spatial-memory performance,4 the fact that pregnenolone enhances cholinergic function (and thus the value of choline) makes it a synergistic substance.

In a second part of the experiment, the researchers observed that smaller amounts of pregnenolone enhanced spatial memory performance, whereas larger amounts were inefficient in this regard. They reported that these results were consistent with previous work suggesting that there is an optimal level of acetylcholine release, one that facilitates memory processes, beyond which higher levels are ineffective. This is consistent with how other nootropics (memory-enhancing supplements) operate. Characteristically, the dose/response curve is steep, although pregnenolone seems to disobey this tendency (see Cognitive Synergy).

The researchers conclude that neurosteroids (such as pregnenolone) "may be of value for reinforcing depressed cholinergic transmission in certain age-related memory disorders." The possible synergy between pregnenolone and choline should be investigated personally.


  1. Darnaudery M, Koehl M, Piazza PV, Le Moal M, Mayo W. Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition. Brain Res 2000 Jan 3;852(1):173-9.
  2. Mathis C, Meziane H, Ungerer A. Models for the study of memory and neurosteroids. Soc Biol 1999;193(3):299-306.
  3. Baxter MG, Frick KM, Price DL, Breckler SJ, Markowska AL, Gorman LK. Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status. Neuroscience 1999 Mar;89(3):771-9.
  4. Darnaudery M, Bouyer JJ, Pallares M, Le Moal M, Mayo W. The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in rats. Brain Res 1999 Feb 13;818(2):492-8.

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator