Dehydroepiandrosterone (DHEA) is a multi-functional steroid that has been implicated in a broad range of biological effects in humans and other mammals. Together with its sulfate ester (DHEA-S), it is the most abundant steroid in humans. DHEA is produced by adrenal glands, but also sythesized de novo in the brain. It acts on the androgen receptor both directly and through its metabolites, which include androstenediol and androstendione, which can undergo further conversion to produce the androgen testosterone and the estrogens estrone and estradiol. DHEA is also a potent sigma-1 agonist. It is considered a neurosteroid.
Synonyms and brand names
Synonyms for dehydroepiandrosterone are:
3-beta-Hydroxy-5-androsten-17-one, 3.beta.-Hydroxyandrost-5-en-17-one, 3beta-hydroxy-5-androsten-17-one, 3beta-hydroxy-androst-5-en-17-one, 3beta-Hydroxy-D5-androsten-17-one, 3beta-Hydroxyandrost-5-en-17-one, 3beta-Hydroxyandrost-5-ene-17-one, 3-beta-hydroxy-etioallocholan-5-ene-17-one , 5-Androsten-3beta-ol-17-one,
Brand names for DHEA include Prastera, Prasterone, Fidelin and Fluasterone. Supplement versions are manufactured from wild Mexican yam.
Dehydroepiandrosterone sulfate
Dehydroepiandrosterone sulfate (DHEAS) 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.
DHEA 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.
Dhea Role
DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. 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.[who?]
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.
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. 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. Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression or to decrease insulin resistance. 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.
In contrast to the non-beneficial effects of DHEA on memory in the elderly, a randomised UK study found that a 7-day course of DHEA (150 mg twice daily) improved episodic memory in healthy young men. In this study, DHEA was also shown to improve subjective mood and decrease evening cortisol concentration, which is known to be elevated in depression. The effect of DHEA on memory appeared to be related to an early activation of the anterior cingulate cortex (ACC) and it was suggested this was due to neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing.
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.
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. However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men. A 2007 study found the DHEA restored oxidative balance in diabetic patients, reducing tissue levels of pentosidine—a biomarker for advanced glycation endproducts.
Some in vitro studies have found DHEA to have an anti-proliferative or apoptotic effect on cancer cell lines. 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.
An anonymous 2002 review, in the French journal Prescrire, concluded: DHEA plasma levels are so low in most animals that they are difficult to measure, hindering studies on DHEA and aging. DHEA had not yet, at the time of writing, been linked to any specific health disorder. Side effects are linked to its androgenic effects, unfavorable lipid metabolism effects, and "possible growth-stimulating effect" on hormone dependent malignancies. "In practice, there is currently no scientific reason to prescribe DHEA for any purpose whatsoever.
A 2005 study, measured serum DHEA in 206 men with type-2 diabetes, and found an inverse relationship between serum DHEA and carotid atherosclerosis in men. The authors say the study "supports the notion that DHEA, which is sold in increasing amount as a food supplement, is atheroprotective in humans, and that androgen replacement therapy should be considered for men with hypogonadism.
A 2006 study supplemented DHEA to men of average 65 years of age, and found that the men experienced significant increases in testosterone and cGMP (Cyclic guanosine monophosphate), and significant decreases in low-density liprotein (LDL). The authors say that the "findings...suggest that chronic DHEA supplementation would exert antiatherogenic effects, particularly in elderly subjects who display low circulating levels of this hormone.
A 2008 study in the Journal of the American Geriatrics Society, June 2008, measured serum DHEA in 940 men and women ranging from age 21 to 88, following them from 1978 until 2005. The researches found that low levels of DHEA-s showed a significant association with shorter lifespan and that higher DHEA-s levels are a "strong predictor" of longevity in men, even after adjusting for age, blood pressure, and plasma glucose. No relationship was found between serum DHEA and longevity for women during the study period. The study did not find a significant difference in longevity until the 15-year follow-up point, which the researchers note may explain why some past research that followed men for less duration found no relationship.
Dhea Disputed effects
In the United States, 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 marketed as over-the-counter dietary supplements. A 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science. Because DHEA is converted to androstenedione and then testosterone, it has two chances to aromatize into estrogen- estrone from androstenedione, and estradiol from testosterone. As such, it is possible for increases in estrogen levels more than testosterone in men.
Dhea Increasing endogenous production
Regular exercise is known to increase DHEA production in the body. Caloric restriction has also been shown to increase DHEA in primates. Some theorize that the increase in endogenous DHEA brought about by caloric restriction is partially responsible for the longer life expectancy known to be associated with caloric restriction.
Dhea Isomers
DHEA (Dehydroepiandrosterone) is really a meaningless term scientifically, since it isn't descriptive of the actual molecule structure and could include a family of structures that are missing hydrogen atoms at one or more points in the molecule. DHEA can have many naturally occurring isomers that may have similar pharmacological effects. Some proven natural isomers of DHEA are 1-dehydroepiandrosterone (shown to be synthesized in pigs), 4-dehydroepiandrosterone (shown to occur in rats), 19NorDHEA (shown to occur in pigs and humans). These isomers are also technically DHEA, since they are dehydro epiandrosterones (removing hydrogens from the epiandrosterone skeleton).
What is DHEA:
The production is at the age of 25 years at the highest, and then steadily falls from up to 5% of the maximum of 85 years. For other steroids, this is not the case. The first precise determination of DHEA production Beach Life, Skiing, Lastminute age occurred in 1958 by Max-Fernand Jayle, biochemists at the University of Paris. Women produce more DHEA than men.
The exact biological role is currently more or less misunderstood. Due to its precursor role include for sex hormones DHEA has been the role of a buffer-related hormone, Which die availability of other steroids influenced. The addition of DHEA in animal and human experiments revealed, however, inter alia, effects against aging, cancer and viral infections.
DHEA has long been known to boost immune function. It is of crucial importance for the development of certain mature immune cells and enhanced antibody production. A new study has found that the number of cells secreting interferon-gamma correlated with serum DHEA levels in men, and that the activity of these cells was associated with DHEA in premenopausal women. Thus, DHEA seems to be involved in the modulation of cytokine production. The same is true for one of its metabolites, androstenediol, which has been shown to protect the bone marrow function and resistance to infection following exposure to radiation in rodents even more effective than DHEA. Androstenediol was also shown to protect against lethal infection with influenza A virus. Since infection produces an increase in cortisol, which in turn suppresses the immune system, it would seem logical to try this counterregulate immunosuppression with antiglucocorticoids as DHEA.
DHEA and cancer:
Between 1972 and 1997, more than 4000 publications worldwide DHEA published until 1991 many studies demonstrated the beneficial effects against various types of cancer, arteriosclerosis, weight reduction and prolonged life span in animals. From 1994, it was mainly the effect in humans explored and revealed comparable results so far.
In the United States and other countries, DHEA is already widely marketed and partially described as a miracle cure. It is from the mostly very positive slip publications that DHEA-GABEN die Simmung improve the sexual activity and increase readiness, stress hormones counteract the muscle condition maintained, strengthen the immune system and cancer and heart disease risk reduction. Yes even against AIDS, osteoporosis and Alzheimer DHEA should be effective.
DHEA is also closely related to brain neurons against age-related degenerative processes such as Alzheimer's coverage. Not only that such degenerative processes most likely to occur if the DHEA levels are low but the concentration of DHEA in the brain is much higher than in blood. Dr. E. Roberts is a specialist in this field of research. He found that small amounts of DHEA enough to count the number of nerve cells to increase the number of their contacts with others to increase their differentiation and in cell cultures anzuregen.DHEA is also found to be the long-term memory in mice trained to improve. DHEA may be a similar role to play in the human brain.
One of the major publications came from Mohammed Kalimi and William Regelson 1990: "The biological role of DHEA" in which scientists in 24 chapters from around the world their findings regarding the potentially most important messenger substance DHEA present. These are impressive. In the preface the editor, you can read:
"DHEA affects diabetes, cancer, tumor formation, skin conditions, fatigue, depression, memory and immune reactions. With this broad range of clinical application, it is surprising, why do not more books about DHEA have been written!"
Early studies from England [Bulbrook, 1962.1971] have shown that DHEA in abnormally low concentrations occurred in women, breast cancer, did die, even up to nine years before the disease was diagnosed. Of 5000 women in the study produced 27 breast cancer. Most of the 27 had extremely low DHEA levels. If low DHEA levels to promote breast cancer, is the reverse acceptable?
The human growth hormone is a peptide hormone (protein), in the pituitary gland (hypophysis) of each healthy people formed in the blood and is secreted, thus all the cells of the body to reach. The outstanding effect of growth hormone in children is the stimulation of body growth. Moreover, it also stimulates the protein, fat and bone metabolism to the growth of the organism through the provision of energy and basic materials to enable. If not enough growth hormone is present or absent entirely, remain short and children's reach as an adult only body sizes up to 140 cm. After completion of growth it is important for the metabolism of the human being the most important "building (anabolic) hormones for muscle, bone and connective tissue. Its significance as a "removal by" hormone in lipid metabolism is in the favorable influence on blood lipid levels by reducing the Artherioskleroserisikos. Medicines with the active growth hormone (somatropin) is the world's ethical pharmaceuticals counted, ie to the drugs whose effectiveness has been proven and for which there is no substitute.
DHEA and cancer information:
Dr. A. Schwartz of Temple University USA found that the addition of DHEA in cell cultures against the toxicity of carcinogenic factors Cancerogenen) preserved. Normally, cultured cells respond to DNA significantly with mutations, changes in the cell appearance and a high mortality rate. When DHEA-GABEN all these effects were significantly reduced. In mice with cancer-causing agents have been treated were those who received no additional DHEA breast cancer. In other studies, a reduction in the tumor rate of up to 80% was observed. [Schwartz, 1981, 1984] The DHEA-known researcher W. Regelsen stated: "Whenever DHEA in a model environment for the development of cancer and Tumorinduzierung was tested, had DHEA Preventive effects."
Although DHEA is currently being tested in human tumors, we do not yet know whether the effects in humans are similar.
This must be said that mice and rats for a long time as the test objects from the studies in humans were used. The results so far have been mostly similar or identical |
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