Saturday, December 22, 2007

The DHEA Breakthrough-Fact or Fiction?

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The DHEA Breakthrough (look younger, live longer, feel better. reduce body fat, build lean muscle mass, restore sexual vigor, boost your immune system, protect against major diseases)...Steven Cherniske, M.S.

What is DHEA? is it natural or synthetic? Extra-ordinary superhormone or a natural adrenaline precurssor to testosterone and estrogene?

Here is the facts


Dehydroepiandrosterone Systematic (IUPAC) name
CAS number 53-43-0
ATC code A14AA07
PubChem 76
Chemical data
Formula C19H28O2
Mol. mass 288.43
Physical data
Melt. point 148.5 °C (299 °F)
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half life 12 hours
Excretion Urinary:?%
Therapeutic considerations
Pregnancy cat. ?

Legal status Commercially available
(US), Rx Only (CA)

Routes Oral
Dehydroepiandrosterone (DHEA), is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin (by an autocrine mechanism). DHEA is the precursor of androstenedione, which can undergo further conversion to produce the androgen testosterone and the estrogens estrone and estradiol. DHEA is also a potent sigma 1 agonist.[1]

Contents [hide]
1 Synonyms and brand names
2 DHEAS (Dehydroepiandrosterone sulfate)
3 Production
4 Role
5 Effects and uses
5.1 Disputed effects
6 Contraindication
7 Increasing endogenous production
8 Legality
9 References
10 External links

[edit] Synonyms and brand names
Synonyms for Dehydroepiandrosterone are: Dehydroisoandrosterone; 3β-Hydroxy-5-androsten-17-one; 3β-Hydroxyandrost-5-en-17-one; Androstenol; Androstenolone; Dehydroisoandrosterone; Hydroxyandrost-5-en-17-one; Prasterone; trans-Dehydroandrosterone.

Brand names for DHEA include Prastera® and Fidelin®.

[edit] DHEAS (Dehydroepiandrosterone sulfate)

Dehydroepiandrosterone sulfate (DHEAS, PubChem 12594) is the sulfated version of DHEA.

This conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestine.

In the blood, most DHEA is found as DHEAS with levels that are about 300 times higher than those of free DHEA. Orally-ingested DHEA is converted to its sulfate when passing through intestines and liver.

Whereas DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation.

From a practical point of view, measurement of DHEAS is preferable to DHEA, as levels are more stable.


Production of DHEA from CholesterolDHEA is produced from cholesterol through two cytochrome P450 enzymes.

Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA.

In humans, DHEA is the dominant steroid hormone and precursor of all sex steroids.

[edit] Role
DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. Its production in the brain suggests that it also has a role as a neurosteroid.[citation needed] As most DHEA is produced by the zona reticularis of the adrenal, it is argued that there is a role in the immune and stress response.[attribution needed]

As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.

Effects and uses

Studies have shown that DHEA is useful in patients with systemic lupus erythematosus. An application of the evidence was discussed by the U.S. Food and Drug Administration in 2001 and is available online.[2] This review also shows that cholesterol and other serum lipids decrease with the use of DHEA (mainly a decrease in HDL-C and triglycerides can be expected in women, p110).

DHEA supplementation has been studied as a treatment for Alzheimer's disease, but was found to be ineffective.[3]

Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression[4][5] or to decrease insulin resistance.[6]

However, a larger placebo-controlled randomized clinical trial reported in the New England Journal of Medicine in 2006 found that DHEA supplementation in elderly men and women had no beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life.[7]

DHEA supplements are sometimes used as muscle-building or performance-enhancing drugs by athletes. However, a randomized placebo-controlled trial found that DHEA supplementation had no effect on lean body mass, strength, or testosterone levels.[8]

A 1986 study found that a higher level of endogenous DHEA, as determined by a single measurement, correlated with a lower risk of death or cardiovascular disease.[9]

However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.[10] A 2007 study found the DHEA restored oxidative balance in diabetic patients, reducing tissue levels of pentosidine—a biomarker for advanced glycation endproducts.[11]

Some in vitro studies have found DHEA to have an anti-proliferative or apoptotic effect on cancer cell lines.[12][13][14] The clinical significance of these findings, if any, is unknown. Higher levels of DHEA, in fact, have been correlated with an increased risk of developing breast cancer in both pre- and postmenopausal women.[15][16]

A 2002 review found that DHEA was difficult to study in an animal model. The authors concluded that there was no evidence that DHEA was beneficial for any of the conditions for which it had been studied to that point, that it was associated with significant side effects, and that based on these findings, "there is currently no scientific reason to prescribe DHEA for any purpose whatsoever."[17]

[edit] Disputed effects
In the United States, dietary supplements containing DHEA or DHEAS have been advertised with claims that they may be beneficial for a wide variety of ailments. DHEA and DHEAS are readily available in the United States, where they are regulated as foods rather than as medications. Given the lack of any proven benefit from DHEA supplementation, a 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science."[18]

[edit] Contraindication
As DHEAS and DHEA are converted to sex steroids, their use is contraindicated in patients with any cancer that is estrogen- or testosterone-dependent.[citation needed]

[edit] Increasing endogenous production
Regular exercise is known to increase DHEA production in the body.[19][20][21] Caloric restriction has also been shown to increase DHEA in primates.[22] Some theorize that the increase in endogenous DHEA brought about by caloric restriction is partially responsible for the longer life known to be associated with caloric restriction.[23]

[edit] Legality
A bill has been introduced, in March 2007, in the U.S. Senate (S. 762) that attempts to classify DHEA as a controlled substance under the category of anabolic steroids. The sponsor is Charles Grassley (R-IA). The cosponsors are Richard Durbin (D-IL), and John McCain (R-AZ).[24] In Canada, a prescription is required to buy DHEA.[25]

[edit] References
^ Romieu, P., Martin-Fardon, R., Bowen, W. D., & Maurice, T. (2003). Sigma 1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward. 23(9): 3572.
^ FDA document regading DHEA and SLE
^ Wolkowitz OM, Kramer JH, Reus VI, et al (2003). "DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study". Neurology 60 (7): 1071-6. PMID 12682308.
^ Wolkowitz OM, Reus VI, Keebler A, et al (1999). "Double-blind treatment of major depression with dehydroepiandrosterone". The American journal of psychiatry 156 (4): 646-9. PMID 10200751.
^ Schmidt PJ, Daly RC, Bloch M, et al (2005). "Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression". Arch. Gen. Psychiatry 62 (2): 154-62. doi:10.1001/archpsyc.62.2.154. PMID 15699292.
^ Kawano H, Yasue H, Kitagawa A, et al (2003). "Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men". J. Clin. Endocrinol. Metab. 88 (7): 3190-5. PMID 12843164.
^ Nair KS, Rizza RA, O'Brien P, et al (2006). "DHEA in elderly women and DHEA or testosterone in elderly men". N. Engl. J. Med. 355 (16): 1647-59. doi:10.1056/NEJMoa054629. PMID 17050889.
^ Wallace MB, Lim J, Cutler A, Bucci L (1999). "Effects of dehydroepiandrosterone vs androstenedione supplementation in men". Medicine and science in sports and exercise 31 (12): 1788-92. PMID 10613429.
^ Barrett-Connor E, Khaw KT, Yen SS (1986). "A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease". N. Engl. J. Med. 315 (24): 1519-24. PMID 2946952.
^ Arnlöv J, Pencina MJ, Amin S, et al (2006). "Endogenous sex hormones and cardiovascular disease incidence in men". Ann. Intern. Med. 145 (3): 176-84. PMID 16880459.
^ Will Boggs. DHEA Restores Oxidative Balance in Type 2 Diabetes. Medscape. Retrieved on 2007-12-14.
^ Yang NC, Jeng KC, Ho WM, Hu ML (2002). "ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells". Life Sci. 70 (17): 1979-88. PMID 12148690.
^ Schulz S, Klann RC, Schönfeld S, Nyce JW (1992). "Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis". Cancer Res. 52 (5): 1372-6. PMID 1531325.
^ Loria RM (2002). "Immune up-regulation and tumor apoptosis by androstene steroids". Steroids 67 (12): 953-66. PMID 12398992.
^ Tworoger SS, Missmer SA, Eliassen AH, et al (2006). "The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women". Cancer Epidemiol. Biomarkers Prev. 15 (5): 967-71. doi:10.1158/1055-9965.EPI-05-0976. PMID 16702378.
^ Key T, Appleby P, Barnes I, Reeves G (2002). "Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies". J. Natl. Cancer Inst. 94 (8): 606-16. PMID 11959894.
^ (2002) "DHEA: the last elixir". Prescrire international 11 (60): 118-23. PMID 12199273.
^ Tokish JM, Kocher MS, Hawkins RJ (2004). "Ergogenic aids: a review of basic science, performance, side effects, and status in sports". The American journal of sports medicine 32 (6): 1543-53. doi:10.1177/0363546504268041. PMID 15310585.
^ Eur J Appl Physiol Occup Physiol 1998 Oct;78(5):466-71
^ Eur J Appl Physiol. 2001 Jul;85(1- 2):177-84
^ J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):B158-65
^ Exp Gerontol. 2003 Jan-Feb; 38(1-2):35-46
^ Roberts E. The importance of dehydroepiandrosterone sulfate in the blood of primates: a longer and healthier life? Biochem Pharmacol. 1999 Feb 15;57(4):329-46.
^ S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid, from Accessed May 9, 2007.
^ Dr. Michael Colgin. The Deal With D.H.E.A. Vista Magazine Online. [1]

[edit] External links
Information on DHEA from the Mayo Clinic
DHEA, from the Skeptic's Dictionary
DHEA in elderly women and DHEA or testosterone in elderly men, published in the New England Journal of Medicine in 2006. "Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life."
[hide]v • d • eAnabolic steroids (A14) (trademark names in brackets)
Androstan (carbon 19 present) Androstadienone • Boldenone undecylenate (Equipoise) • 4-Chlordehydromethyltestosterone (Turinabol) • Clostebol • Desoxymethyltestosterone (Madol) • DHEA • DHT • Drostanolone (Masteron) • Fluoxymesterone (Halotestin) • Furazabol (Miotolan) • Methandrostenolone (Dianabol) • Methenolone • Mesterolone (Proviron) • Methenolone enanthate (Primobolan) • Mestanolone • Norethandrolone • Oxandrolone (Anavar) • Oxymetholone (Anadrol) • Oxymetholone (Anadrol-50) • Quinbolone (Anabolicum Vister) • Stanozolol (Winstrol) • Testosterone
Estren (carbon 19 absent) Ethylestrenol • Mibolerone (Cheque Drops) • Nandrolone (Deca Durabolin) • Norbolethone (Genabol) • Oxabolone cipionate • Tetrahydrogestrinone (The Clear) • Trenbolone (Fina)

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