Pregnenolone hormone precursor
Pregnenolone hormone precursor
Hot on the heels of: melatonin, DHEA and Mexican Wild Yam is another hormonal supplement poised to take the health food market by storm.
In fact it enjoyed a brief period of use in arthritic diseases before the Second World War when it was overtaken by cortisone (which later proved to have serious long-term, side-effects).
Commonly called the "grandmother" of all steroid hormones, the estrogen-deficient post-menopausal woman may be the primary target but there are suggestions that a broader spectrum of the population, including older men and people suffering from immune disorders may also benefit.
It is considered to be the precursor to DHEA which was, itself, only recently lauded as the precursor to steroid hormones and dubbed: "mother".
As the name implies, it relates to pregnancy and progesterone but also, via DHEA, to the male and adrenal hormones as well.
The plasma levels of deoxycorticosterone sulfate in near-term pregnant women are approximately 100 times greater than levels in men, or non-pregnant women. The source has only recently been elucidated. It apparently derives from fetal plasma pregnenolone -3, 21 disulfate. (Corsan, 1997)
It may also have a role in the activation of immune defenses. (Doostzadeh, 1996)
It has recently been shown that pregnenolone and pregenolone sulfate can be administered by IV and cross the BBB (blood brain barrier) raising levels in the brain (especially the hypothalamus). (Wang, 1997)
Dr. Sahelian is one physician who always seems to be ready with a book on the latest "hot" product. So early in the history of a product, there is very little else to go by. He identifies the following people as likely beneficiaries of his latest text: "Pregnenolone: A Practical Guide".
This is not, actually, a new product (at least so far as the pharmaceutical manufacturers are concerned) and the patent expired years ago, so research tends to be done in animal experiments, rather than the more expensive human trials required when a new drug is about to be approved by the FDA and launched on the market.
The current interest derives from nutritional product manufacturers, health food stores and multi-level marketing companies, each of whom have a version of the product.
Chronic Fatigue syndrome
More aggressive marketing requires the heaviest dosage in order to sell the most pills. Some companies have gone for a conservative pill which may be taken in multiples, like one, two or three 10 mg capsules. Other companies have opted for asingle dose at a higher concentration e.g. 100 mg. Still other companies recommend a variety of sources: pills as well as lotions (which, you will recall has proven extremely popular for DHEA and Wild Yam creams).
Usage of the product, originally, for arthritis diseases was in the range of 200 - 500 mg per day.
It is possible to have tests done at a physician’s office, or even with a home kit.
The common-sense approach is to start with a small dosage and work up until you notice a difference over a few days or weeks. If you don’t notice a difference, simply stop taking the product.
If you do notice a difference, you might try reducing your dosage, to see if a lower maintenance level is still successful.
A typical range for a nutritional supplement is probably between 5 - 100 mg. Therapeutic dosages beyond that should have some objective basis.
Transdermal cream is a topical product that delivers the steroid hormone precursers DHEA and Pregnenolone to the body via the skin. Transdermal application is effective because these hormones are small fat-soluble molecules that can easily be absorbed across the skin and stored in the fat tissues, from there they are diffused into the capillaries and then taken up directly into the blood ciculation..
Transdermal delivery systems can be more efficient than oral supplementation because when taken orally, the hormone has to be passed through the stomach and then transported to the liver where it is further metabolized with much of it being excreted in the bile.
Dosages-1/4 to 3/4 teaspoon depending on the individual- each 1/2 teaspoon contains 22 mg of Pregnenolone and 8 mg of DHEA.
Safety & Toxicity
Efforts are being made to place supplementation on an objective basis, so that home saliva kits are being marketed so that people may gauge their personal level of deficiency, if any.
Correspondingly, supplements may be taken and the test repeated to gauge how much is enough to reach targeted levels.
Certainly, double the suggested maximum nutritional amount has been used in prescriptions in the past without sufficient ill effect to prevent the product form being sold over-the-counter.
As the popularity increases, any subtle problems should surface quite rapidly. This is especially so as if it is successful, physicians and the pharmaceutical companies will want to restore it to a prescription status, in order to reap the dividends. Current therapy is only around a dollar a day.
Akamatsu T et al: Menopause related changes of adrenocortical steroid production. Asia Oceania J Obstet Gynaecol, 1992 Sep, 18:3, 271-6.
Corsan, GH et al., Origin of deoxycorticosterone sulfate (DOC-SO4) in plasma of pregnant women: pregnenolone-3,21-disulfate is a placental precursor of DOC-SO4. J. Steroid Biochem. Mol. Biol. 1997, 60(5-6):331-337.
Davison, R.: Effects of delta 5 pregnenolone in rheumatoid arthritis. Arch. Int. Med. 1950, 85: 365 - 388.
Doostzadeh, J et al., Pregnenolone-7 beta-hydroxylating activities of yeast-expressing mouse cytochrome P450-1A1 and mouse-tissue microsomes. Eur. J. Biochem. 1996, 242(3):641-7.
Flood, J. et al: Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic structures. Proc. Nat. Acad. Sci. USA. 1995, 92:10,806 - 10,810.
George MS et al: CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. Biol Psychiatry, 1994 May 15, 35:10, 775-80.
Guth, L. et al: Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc. Nat. Acad. Sci. USA. 1994, 91(25): 12,308 - 12,312.
Hedman M et al: Low blood and synovial fluid levels of sulpho-conjugated steroids in rheumatoid arthritis. Clin Exp Rheumatol, 1992 Jan-Feb, 10:1, 25-30.
Lavall?e B et al: Formation of pregnenolone- and dehydroepiandrosterone-fatty acid esters by lecithin-cholesterol acyltransferase in human plasma high density lipoproteins. Biochim Biophys Acta, 1996 Feb 16, 1299:3, 306-12.
Meziane H et al: The neurosteroid pregnenolone sulfate reduces learning deficits induced by scopolamine and has promnestic effects in mice performing an appetitive learning task. Psychopharmacology (Berl), 1996 Aug, 126:4, 323-30.
Morfin R et al: Neurosteroids: pregnenolone in human sciatic nerves. Proc Natl Acad Sci U S A, 1992 Aug 1, 89:15, 6790-3.
Muto M et al: Successful treatment of vitiligo with a sex steroid-thyroid hormone mixture. Dermatol, 1995 Oct, 22:10, 770-2.
Pascal, A.: Pregnenolone. At Press.
Pincus, G. & Hoagland, H.: Effects of amdinistered pregnenolone on fatiguing psychomotor performance. J. Aviation Med. 1944, 15: 98 - 115.
Provost PR et al: Transfer of dehydroepiandrosterone- and pregnenolone-fatty acid esters between human lipoproteins. J Clin Endocrinol Metab, 1997 Jan, 82:1, 182-7.
Purohit A et al: Inhibition of steroid sulphatase activity by steroidal methylthiophosphonates: potential therapeutic agents in breast cancer. J Steroid Biochem Mol Biol, 1994 Apr, 48:5-6, 523-7.
Regelson, W. & Colman, C.: Pregnenolone: The Superhormone Promise. Simon & Schuster, N.Y. 1996.
Roberts, E. Pregnenolone from Selye to Alzheimer and a model of the pregnenolone sulfate binding site on the GABA-A receptor. Biochem. Pharmacol. 1995, 49: 1- 16.
Sahelian, R.: Pregnenolone: A Practical Guide. Dello. 1996.
Steiger A: Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res, 1993 Jul 2, 615:2, 267-74.
Wang M et al., Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one. J Clin Endocrinol Metab, 1996 Mar, 81:3, 1076-82.
Wang M et al., The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. J. Steroid Biochem. Mol. Biol. 1997, 62(4):299-306.
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