DHEA (dehydroepiandrosterone) is popularly viewed as a nutritional supplement, but is actually a hormone. One of the many steroid hormones secreted by the adrenal gland, DHEA was discovered in 1934. However, it is a precursor hormone-a hormone that is converted into several other hormones by the body-and for some time was thought to be less important than these metabolized end products. We now know that that this hormone has many functions, including support of the immune system; repair and maintenance of tissues; reduction of allergic reactions; and, possibly, the prevention of certain forms of age-related diseases, as well as a slowing of the aging process itself.
7-oxo-DHEA Acetate (7-KETO-ZYME) is not converted to sex hormones – that is, it will not convert to testosterone or estrogen and is approximately 2.5 times more active than plain DHEA. This will be discussed below.
FUNCTIONS AND USES
To understand how DHEA works within the body, it is important to first know that after DHEA is secreted by the adrenal glands, it is metabolized into DHEAS (dehydroepiandrosterone sulfate) in the liver, and then further converted to male hormones known as androgens (testosterone, dihydrotestosterone, and androstenedione), and female hormones known as estrogens (estrone and estradiol). Although the mechanism by which this conversion takes place isn’t exactly known, it appears to be influenced by age, gender, and age-related diseases.
There are conflicting reports as to how much DHEA is made by the body. It is estimated that we have, on average, a range of 1 to 2 milligrams of DHEA and 10 to 15 milligrams of DHEAS circulating in the blood.
As we age, our levels of DHEA and the male and female hormones significantly decline, along with those of other hormones, including the growth hormone. It is estimated that by age sixty, DHEA levels are a third or less of those in young adults. At age eighty, people have between 80 and 90 percent less DHEA in their blood than they had at the age of twenty-five. Many researchers believe that these reduced hormone levels are closely associated with aging-related problems, such as shrinkage of muscle mass, diminished immune function, and memory loss. In fact, the majority of human studies on DHEA have focused on aging and the diseases associated with aging.
In one study, men and women of ages forty to seventy were given 50 milligrams of DHEA daily for a six-month period. Within two weeks of the start of DHEA therapy, DHEA and DHEAS levels were restored to those of young adults. This supplementation resulted in a remarkable increase in perceived physical and psychological well-being for 67 percent of the male subjects and 84 percent of the female subjects, without any reported side effects.
Other studies have shown that DHEA or DHEAS given in appropriate replacement doses increases muscle strength and lean body mass, activates immune function, and enhances the quality of life in aging men and women, with no significant adverse effects. In yearlong trials with elderly men and women, subjects reported enhanced overall feelings of wellness, improved sleep, and diminished joint soreness. Moreover, in animal studies, DHEA has been shown to restore memory function by encouraging neurite growth in the brain.
Often, the influenza vaccine does not benefit those it is targeted to help-the elderly. The reason is that many individuals over the age of sixty no longer have the immune response necessary to make the antibodies to the vaccine.
In one study of subjects, ages sixty-five and older, one group received oral DHEAS before receiving a flu vaccine. The immune response to the vaccine was greater in the group that received DHEAS than in the supplemented group, suggesting that DHEAS supplementation may be a useful adjunct to the flu vaccine. However, in a similar study, supplementation with DHEAS did not enhance the immune response to a tetanus injection. Therefore, the ability of DHEAS to bolster the immune response to vaccines appears to be specific, and must be tested for each vaccine.
In another study, researchers evaluated the effects of DHEA on immune function in postmenopausal women. Women who received the DHEA supplement demonstrated improved levels of the cells needed for immune response. This beneficial action may account for the clinical and experimental evidence of DHEA’s anticancer effect.
Many AIDS patients are using high levels of DHEA, as in advanced stages of AIDS; patients have extremely low DHEA blood levels. Although anecdotal reports indicate that DHEA may strengthen the immune system, relieve fatigue, and build muscle, experimental studies do not exist at this time.
Another immune-related disorder that has responded to DHEA supplementation is a condition known as hereditary angioneurotic edema (HAE). HAE is characterized by an allergic reaction that results in swelling of subcutaneous (beneath the surface of the skin) or submucous (beneath the mucous membrane) tissues. These patients have a deficiency of the Cl esterase inhibitor protein, which is the part of the immune response that normally protects against such attacks and inflammation. Eight patients with severe attacks of HAE were given DHEAS for three to twenty-eight months. Supplementation resulted in a dramatic improvement of clinical symptoms and a moderate increase in Cl inhibitor protein concentrations.
Animal studies have demonstrated that DHEA has anticancer properties. For example, when mice were exposed to chemicals that would normally induce breast cancer as well as other types of cancer, those animals that received DHEA did not develop cancer. Other animal studies have demonstrated that DHEA supplementation inhibits skin and lung cancer, as well.
Both human and animal studies have indicated that DHEA plays a role in cardiovascular health. In one study, a group of men received 50 milligrams of DHEA or a placebo for twelve days. The results suggested a natural “blood thinning” effect that may help prevent heart disease. In a twelve-year follow-up study of 143 middle-aged men, those subjects with high DHEAS levels in their blood suffered half as many cases of heart disease as did those with low DHEAS levels. However, the women with higher DHEA levels had a slightly higher risk of heart disease.
As we age, we generally experience a decline in insulin sensitivity that causes glucose to remain in the blood in high levels. Thus, aging is associated with an increased incidence of diabetes.
In one study, a group of postmenopausal women were given 50 milligrams of DHEA daily for three weeks. Their insulin tissue sensitivity increased and their serum triglycerides were lowered, indicating improved glucose handling. Some researchers theorize that since DHEA levels are very low in patients with insulin-dependent diabetes, replacement of DHEA may prevent or even treat the atherosclerosis (hardening of the arteries) that is often associated with this type of diabetes.
DHEA has been shown to be beneficial in women with Systemic Lupus Erythematosis. In one study, female patients given 200 milligrams of DHEA for three to six months experienced overall clinical improvement, enabling them to reduce their medication. DHEA may hold promise as a safe, effective treatment for lupus patients.
RDIs AND DEFICIENCIES
There are no established RDIs for DHEA, and no deficiency symptoms have been identified.
Food Sources: At this time, no food sources of DHEA have been identified.
Although some studies have used DHEA while others have used DHEAS, only DHEA is available as a dietary supplement. You will generally find it in the form of tablets and capsules in doses beginning at 5 milligrams.
OPTIMUM DAILY INTAKE-ODI
There is no ODI for DHEA. Since DHEA is a hormone that can influence the production of androgens and estrogens, most practitioners feel it is imperative that DHEA be used only under professional advice. Before beginning supplementation, it is best to have your physician first run a blood test of the following: DHEA; DHEAS; estradiol, estrone, and estriol, the three types of estrogen; and serum and free testosterone. Men with prostate conditions should have a physician measure their levels of dihydrotestosterone and PSA (prostate specific antigen, a marker for prostate cancer). DHEA should be used with extreme caution in men with prostate conditions, since it may raise levels of the androgens, which are the culprits in prostate disease. The same is true of women with disorders related to excessive estrogen. Once supplementation begins, all hormone levels should be retested within three weeks to evaluate the effects of the DHEA supplement in order to adjust the dosage as necessary.
The purpose of using DHEA is to raise levels of the measured hormones so that they fall within normal ranges. You do not want to take so much DHEA that your hormone levels exceed the normal reference range. It is best to start with low doses of DHEA-5 milligrams for women, and 10 milligrams for men-and slowly increase the levels by 5 to 10 milligrams each week until the desired result is achieved. Use the lowest dosage of DHEA needed to achieve results. Maximum doses are usually 25 milligrams for women and 50 milligrams for men. In studies, much higher doses have been used for some medical conditions, such as lupus. However, we still recommend starting with a lower dose and increasing slowly over time. Keep in mind that most studies have D” Cined the effects of DHEA in individuals over the age of sixty-individuals who have comparatively low levels of DHEA.
Remember: If you have a medical condition, please consult your physician before taking supplements.
TOXICITY AND ADVERSE EFFECTS
Serious side effects of DHEA supplementation have not been reported in human studies. Since high levels of DHEA stimulate the production of androgens, some side effects associated with high androgen levels have been reported, including acne and excessively oily skin, hair growth in women, deepening of the voice, and mood changes. These side effects are reversible when DHEA is discontinued. Only one animal study demonstrated liver cancer in rats given DHEA in doses far above what would normally occur in the animal.
DHEA (dehydroxyepiandrosterone) is a hormone made by the adrenal glands, testes and ovaries. Like other steroid hormones, DHEA is fabricated from cholesterol and is released into the bloodstream where it is the most abundant of this hormone class. However, unlike the other steroid hormones, production of DHEA peaks between the ages of 25 and 30, then declines with increasing age. DHEA possesses complex, multiple roles in health and disease; however, its physiologic role is still not clear. Research suggests that low blood levels of DHEA are linked to CARDIOVASCULAR DISEASE in men. Animal studies provide an insight as to how this can occur: DHEA treatment decreases fat synthesis and the formation of LDL (LOW-DENSITY LIPOPROTEIN, the less desirable form of cholesterol). In addition, DHEA may reduce the risk of OSTEOPOROSIS and several forms of cancer. DHEA also can prevent the development of diabetes in mice with a predisposition to this disease. On the other hand, high DHEA levels in postmenopausal women can lead to increased abdominal fat, resistance to the blood-sugar lowering action of INSULIN and increased risk of cardiovascular disease.
DHEA supports a healthy immune response. Low DHEA blood levels increase the risk of infection. DHEA may be effective against autoimmune diseases like RHEUMATOID ARTHRITIS and lupus, in which the immune system attacks the body. DHEA apparently increases the levels of a growth factor (Insulin-like Growth Factor) that boosts cell metabolism and helps regulate immunity. In men DHEA administration may activate T-cells called natural killer cells that combat viruses. Current research suggests that this powerful hormone plays a role in the aging process and administering DHEA to older men and women can increase the sense of physical and mental well being. However, this hormone does not prevent aging.
Ebeling, Peretti, and Koivisto, “Physiological importance of dehydroepiandrosterone,”” Lancet, 343 (1994), pp. 1479-8.
The chemical name of the 7-Keto metabolite of DHEA is 3-Acetoxyandrost-5-en-7,17-dione (also referred to as 7-oxo-DHEA Acetate). It is a natural occurring DHEA metabolite in the body. Structurally, 7-KetoTM is almost identical to DHEA, however, the activity of 7-Keto has been reported to be 2.5 times that of DHEA. There are other key differences as well.
DHEA (Dehydroepiandrosterone), along with cortisol, is produced by the adrenal glands.
The sulphated form of DHEA (DHEA-S), which is the most plentiful adrenal steroid circulating in the bloodstream, and is generally believed to be metabolically inactive, is converted by cells to DHEA. Secretion of DHEA/DHEA-S increases around the ages of 6 to 8, reaches its maximum somewhere between the ages of 20-30, and progressively decreases from then on.
At age 70, serum DHEA-S may be only 20% of peak levels and will continue to decrease as age progresses.
The health related properties of DHEA have been documented in scientific publications too numerous to mention. The diversity of beneficial effects have been associated with lower incidences of diabetes, dementia and obesity. Immune enhancing effects have been observed and noted as well. They include a strong inverse correlation between serum DHEA-S levels and IL-6 (interleukin 6) levels. A study by Straub, et. al. reveals that as we age, IL-6 levels tend to increase, while DHEA-S levels decrease. Decreased serum DHEA concentrations “during aging or inflammatory diseases are paralleled by a significant increase in IL-6 production.” The study concludes that the decrease in DHEA levels is harmful, especially during chronic inflammatory conditions. Research also indicates DHEA plays a roll in age related increased insulin levels, insulin resistance and blood glucose.
7-Keto supplies a natural metabolite of DHEA normally found in the body, which cannot be bio-transformed into testosterone or estrogens. 7-Keto has been studied for safety and shown not to be mutagenic, nor did it result in adverse effects in primate studies, even at high human equivalencies.
*** Concerns associated with DHEA supplementation do exist. The greatest concern relates to the ability of tissues to convert DHEA to androgens such as testosterone, or estrogens such as estrone or estradiol. Androgen increases in women may be associated with mild effects such as excess facial hair, to more serious concerns such as hyperglycemia or insulin resistance. A published report cited a male with an increase in estradiol, combined with a decrease in testosterone.
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3. Regelson, W. & Kalimi, M. (1994) “Dehydroepiandrosterone (DHEA) – the multifunctional steroid” Ann NYAcad Sci 719: 564-75.
4. Straub, R. et. al. (1998) “Serum DHEA and DHEA sulfate are nega-tively correlated with serum interleukin-6 (IL-6) and DHEA inhibits
IL-6 secretionfrom mononuclear cells in man in vitro ” J Clin Endocrino. Metab 83: 2012-17.
5. Jakubovvicz, D. et al (1995) “Effect of dehydroepiandrosterone on cyclic-guanosine monophosphate in age-advanced men” Ann NY Acad Sci 774: 312-15.
6 Ebeling, E. & Koivisto, V, (1994) “Physiological importance ofdehydroepiandrosterone ” Lancet 343: 1479-81.
7. Bloch, M. et. al. (1999) “Dehydroepiandrosterone treatment o fmidlife dysthyima ” Biol Psychiatry 45: 1533-41.
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