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Life Extension Magazine

LE Magazine June 2004
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Recharge With Pregnenolone
This little-known hormone fights fatigue, boosts memory, and more.
By Dave Tuttle

Counteracting Depression
Another likely benefit of pregnenolone is a reduction in depression and related disorders. Historically, the relatively high incidence of depression in older adults has been attributed to the loss of loved ones or the negative psychological effects of debilitating disease. Although these factors can certainly influence a person’s mood, in recent years scientists have found that depression is usually associated with levels of serotonin and other neurotransmitters. For example, the antidepressant Prozac® increases serotonin levels in the brain by inhibiting the reuptake of this neurotransmitter. The inhibition of GABA release is also thought to enhance mood by preventing the brain from becoming too sluggish and lethargic. Pregnenolone’s ability to control GABA levels strongly suggests that this hormone may be a valuable addition to the arsenal of antidepressant medications, especially considering its lack of side effects.

While human studies of pregnenolone supplementation have not been completed, compelling evidence suggests that pregnenolone plays a role in depression. In a study of 27 patients with depression and 10 healthy volunteers, the depressed subjects had lower levels of pregnenolone in their cerebrospinal fluid than the healthy individuals.13 Cerebrospinal fluid circulates in the spinal column and brain, indicating that the brains of the depressed patients were exposed to less pregnenolone than those of the healthy subjects. In another study that matched 12 healthy controls with 12 men who had generalized social phobia and were not taking medication, concentrations of pregnenolone sulfate were significantly lower in the plasma of the patients with social phobia, again implying that pregnenolone plays a role in mood states.14

Help for Spinal Cord Injuries
Because pregnenolone is naturally found in the cerebrospinal fluid, researchers have sought to determine whether it can help accident victims with spinal cord injuries. Pregnenolone was found to promote recovery when used in combination with other drugs.15

Researchers gave pregnenolone, indomethacin (an anti-inflammatory substance), and bacterial lipopolysaccharide (a stimulator of cytokine secretion) to rats both individually and in combination for 21 days. While the use of indomethacin and lipopolysaccharide eased the histopathological damage to some extent, there was little recovery of motor function. Adding pregnenolone to the mix produced a striking reduction in histopathological damage, and the tissue was spared from secondary injury (a common occurrence with spinalcord victims when the components of the inflammatory response become destructive). This three-way combination worked so well that 11 of the 16 animals were able to stand and walk after 21 days, four of them almost normally. The survival rate improved as well, possibly due to the protection that pregnenolone offered against the toxic effects of the other two drugs. Pregnenolone also increased the vascularization of the spared tissue and made the cellular matrix denser, while reducing the extent to which cavities formed on the injured tissue.

The researchers concluded that pregnenolone facilitated recovery by giving rise to the greatest number of other hormones, which are known to assist with coordinative processes within and between the neural, metabolic, and immune systems. Because of its dual action in inhibiting GABA release and boosting glutamate levels, pregnenolone can “exert remarkable synergistic amplification of excitatory transmission,”15 triggering the cascade of reactions needed for cell recovery.

Pregnenolone holds great promise in helping accident and trauma victims recover from their injuries. While the extent of benefit still must be quantified, it seems clear that the cascade of reactions produced by pregnenolone may be valuable in addressing a variety of medical conditions.

Benefits for Rheumatoid Arthritis
Pregnenolone has been shown to relieve the symptoms of rheumatoid arthritis. As noted earlier, this hormone alters the permeability of cell membranes, lessening swelling and associated pain with a resulting increase in strength. Pregnenolone also may play a role in reducing the formation of COX-2, which would counteract the availability of various inflammatory compounds.

A number of studies have confirmed that pregnenolone has dramatic anti-arthritic effects, though the daily oral dosage required—approximately 500 mg—is significantly more than the dose needed to realize mental improvements.4 Pregnenolone is most helpful in the initial stages of arthritis before the pathological process has progressed too far. Moreover, a comparative study of cortisone and pregnenolone found that improvements lasted longer after the study ended when pregnenolone was administered. Because cortisone has several negative side effects, concurrent use with pregnenolone should permit a reduction in the cortisone dosage, helping to reduce the suffering of persons with rheumatoid arthritis. More research is needed, however, to determine the ideal combination dosage. Unfortunately, pregnenolone is not beneficial for osteoarthritis, a condition in which little inflammation exists.

Summary
Physicians have recommended hormone-replacement therapy to older individuals for many years. Usually, however, the hormones replaced are the end-product hormones: testosterone or estrogen. Recent research suggests that there may be another way. By providing your body with the mother of hormones—pregnenolone—you can let your body decide through its various feedback mechanisms which hormones it needs. If more DHEA is required, the supplemental pregnenolone will be converted to this hormone, and if estrogen or testosterone is in short supply, the pregnenolone molecule will be altered to produce the optimal amount. If your physiological requirement is a combination of hormones, this, too, can be achieved.

By its very nature, pregnenolone works with your body to achieve optimal health and longevity. Pregnenolone’s many functions underscore its role as one of the most important hormones in the human body. Pregnenolone reduces fatigue and increases endurance. It also provides the brain with the hormonal and neurotransmitter support it needs to retard memory loss, thus helping to improve concentration and focus. Moreover, it helps those with arthritis, depression, and traumatic injuries.

Although pregnenolone has long been overlooked because it is “upstream” on the hormone pathway, its many benefits to human health suggest that this vital hormone has just begun to receive the attention it so richly deserves.

References

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2. Havlíková H, Hill M, Hampl R, Stárka L. Sex- and age-related changes in epitestos- terone in relation to pregnenolone sulfate and testosterone in normal subjects. J Clin Endocrinol Metab. 2002 May;87(5):2225-31.

3. Lanthier A, Patwardhan VV. Sex steroids and 5-en-3b-hydrosteroids in specific regions of the human brain and cranial nerves. J Steroid Biochem. 1986 Sep;25(3):445-9.

4. Roberts E. Pregnenolone from Selye to Alzheimer and a model of the pregnenolone sulfate binding site on the GABAa receptor. Biochem Pharmacol. 1995 Jan 6;49(1):1-16.

5. Mayo W, George O, Darbra S, et al. Individual differences in cognitive aging: implication of pregnenolone sulfate. Prog Neurobio. 2003 Sep;71(1):43-8.

6. Regelson W, Colman C. The Superhormone Promise: Nature’s Antidote to Aging. New York, NY: Simon & Schuster; 1996.

7. Roberts E, Sherman MA. GABA—the quintessential neurotransmitter: electroneutrality, fidelity, specificity, and a model for the ligand binding site of GABAa receptors. Neurochem Res. 1993 Apr;18(4):365-76.

8. Darnaudéry M, Koehl M, Pallarés M, Le Moal MJ, Mayo W. The neurosteroid preg- nenolone sulfate increases cortical acetyl- choline release: A microdialysis study of freely moving rats. J Neurochem. 1998 Nov;71(5):2018-22.

9. Vallée M, Mayo W, Darnaudéry M, et al. Neurosteroids: deficient cognitive perfor- mance in aged rats depends on low preg- nenolone sulfate levels in the hippocampus. Proc Natl Acad Sci USA. 1997 Dec 23;94(26):14865-70.

10. Vallée M, Mayo W, Le Moal M. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Rev. 2001 Nov;37(1-3):301-12.

11. Darnaudery M, Pallares M, Piazza PV, Le Moal M, Mayo W. The neurosteroid preg- nenolone sulfate infused into the medial sep- tum nucleus increases hippocampal acetyl- choline and spatial memory in rats. Brain Res. 2002 Oct 4;951(2):237-42.

12. Mayo W, Le Moal M, Abrous DN. Pregnenolone sulfate and aging of cognitive functions: Behavioral, neurochemical, and morphological investigations. Horm Behav. 2001 Sep;40(2):215-7.

13. George M, Guidotti A, Rubinow D, Pan B, Mikalauskas K, Post R. CSF neuroactive steroids in affective disorders: pregnenolone, progesterone and DBI. Biolog Psychiatry. 1994 May 15;35(10):775-80.

14. Heydari B, Le Melledo JM. Low preg- nenolone sulfate plasma concentrations in patients with generalized social phobia. Psychol Med. 2002 Jul2;32(5):929-33.

15. Guth L, Zhang Z, Roberts E. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Natl Acad Sci USA. 1994 Dec 6;91(25):12308-12.