DHEA
DHEA (dehydroepiandrosterone) is a hormone secreted from the adrenal glands. It is a precursor of the sex hormones (estrogen and testosterone). DHEA-S has recently been shown to have beneficial effects on memory, stress, anxiety, sleep and depression. Therefore, the deficiency of DHEA-S might be related to the symptoms in patients with CFS. (van Rensburg, Potocnik et al. 2001) DHEA has been reported to improve energy levels in chronic fatigue
patients. (Kuratsune, Yamaguti et al. 1998b)
One study showed the value of DHEA and vitamin C infusion treatment in the control of chronic fatigue syndrome. (Kodama, Kodama et al. 1996)
A study of 15 subjects with CFS, 15 subjects with major depression, and 11 healthy subjects found that DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group. DHEA-S levels, but not DHEA, were lower in the depressives. The authors concluded that DHEA has a potential role both therapeutically and as a diagnostic tool, in CFS. (Scott, Salahuddin et al. 1999)
Another study of DHEA levels in 22 CFS patients and 14 healthy controls found normal basal DHEA levels, but a blunted serum DHEA response curve to ACTH (adreno-corticotropic hormone) injection. ACTH normally stimulates the adrenal glands to secrete DHEA. The authors concluded that endocrine abnormalities play a role in CFS and that a relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS. (De Becker, De Meirleir et al.
1999)
http://www.newtreatments.org/fromweb/licoriceprotocol.txt
The Low DHEA Connection DHEA levels are also controlled by the same factors that control the production of cortisol so that both should be low is only a natural conclusion. If you havelow cortisol--you have low DHEA! Ifyou have low DHEA--you have low cortisol! DHEA is much easier to measure than cortisol so if there is any single test you should seek out it should be plasma DHEA levels. Fact is, findings of low levels of DHEA in CFS might even be considered as a marker for CFS according to researchers at Trinity College Medical School inDublin, Ireland (abstract). It should also come as no surprise that DHEA has been found low in this illnesses by every effort to measure the hormone to date(abstract)! A blunted DHEA response to ACTH has also been noted in chronic fatigue syndrome (abstract).
DHEA is quantitatively the most abundant hormone in humans and mammals, with a wide variety of physiological effects, including major regulatory effects uponthe immune system (abstract).Two of the most striking aspects of DHEA are a steady decline in DHEA with age and a significant deficiency in DHEA in patients with several major diseases, including chronic fatigue syndrome,cancer, atherosclerosis, and Alzheimer's disease The hormone is secreted in a non-sulfated (DHEA)and sulfated form (DHEA-S). The two are apparently interchangeable, and it appears likely that its physiological effects are achieved by derivative molecules that have yet to be identified. DHEA hasother positive effects on immunity (abstract). Theneurohormone also inhibits IL-6, known to beupregulated in CFS (abstract) (abstract). Research has shown that DHEA benefits people withLupus (abstract). The release of DHEA and cortisol from the adrenal glands is controlled by ACTH. ACTH is controlled by CRH. Recent evidence has been publishedindicating that there might be a defect in CRH secretion from the pituitary gland (abstract) in CFS.Research done in women with fibromyalgiaalso indicates a HPA axis problem (abstract). So, in summary, the evidence indicated that the hyperimmunity in CFS is caused by secondary hypoadrenalism due to a blunted response to CRH andvasopressin and the resulting low cortisol and DHEA. Yet, many doctors still refuse to supplement with hydrocortisone and/or DHEA! They site a recent study sponsored by NIH which indicated that people withchronic fatigue syndrome treated with daily low doses of hydrocortisone fail to report a significant recovery (link) (abstract).
http://www.cfids-cab.org/cfs-inform/Hpa/finckh.etal05.txt
DHEA does not improve quality of life, pain, fatigue, cognitive function, mood, or functional impairment in FM.
http://www.cfids-cab.org/cfs-inform/Hpa/scott.etal00.txt
A preliminary study of dehydroepiandrosterone response to low-dose ACTH in chronic fatigue syndrome and in healthy subjects http://www.cfids-cab.org/cfs-inform/Hpa/vanrensburg.etal01.txt In the present study, significantly lower DHEAS levels were found in CFS patients. Impaired production of steroids has previously been demonstrated inCFS [10]. Decreased DHEA(S) has also been implicated in Alzheimer's disease [41], in severe illness, systemic lupus erythematosus, and anorexianervosa [19]. Plasma DHEAS levels correlate with many parameters of physical and mental well being, for example, in HIV-positive patients, DHEAS levelsdecrease as the disease progresses towards AIDS, the decrease occurring as symptoms (including dementia [36]) develop [19]. Immunological abnormalitiesin CFS [13, 15 and 39] may also be associated with decreased levels of DHEAS [29]. In addition, DHEA and DHEAS are excellent free radical scavengers[44]. The significant inverse correlation between DHEAS and Fe found in the present study could possibly be linked to the aberrations in cytokine production inCFS [13]. DHEA(S) has an immunoregulating function, its primary target being stimulation of the TH-1 subclass of the CD4+ T cell population, leading toincreased lymphokine interleukin-2, while inhibiting interleukin-6 production [29]. Higher interleukin-6 levels have been found in patients with CFS [13]and in anaemia of chronic disease of unknown origin [26]. A prolonged activation of the immune system may also cause continual sequestration of Fe,rendering it unavailable for other body functions [7 and 38], while simultaneously increasing oxidative damage [2]. The high cholesterol values found in patients with CFS may be due to a mechanism of negative feedback control in the synthesis of DHEA fromcholesterol: DHEA inhibits isoprenylation by depletion of endogenous mevalonate, a precursor of cholesterol synthesis [35]. Thus, decreasedconcentrations of DHEA may be accompanied by increased cholesterol concentrations. CONCLUDING REMARKS CFS manifests with both cognitive and somatic symptoms. Metals and adrenal steroids have been shown to play a role both in brain function anddysfunction, as well as the modulation of cytokines. Hence the results obtained in the current study reinforce the idea that the widespread symptomsof CFS would be better explained by a model indicating that the primary dysfunction is central rather than peripheral in origin. The pivotal part ofthis dysfunction may be the low serum Fe, reflecting exhaustive utilization (externally by sweating and internally by chronic inflammation), but notadequately replenished from food sources or body stores for some unknown reason. Normally a shortage of iron would result in an increased production ofTf to meet the body's demands, but in CFS the message for increased Fe uptake is thwarted. http://home.caregroup.org/clinical/altmed/interactions/Nutrients/DHEA.htm Summary
DHEA (Dehydroepiandrosterone)
forms/synonyms: DHEA, prasterone; DHEA-S
chemical name: Dehydroepiandrosterone; Dehydroepiandrosterone-sulfate.
overview of interactions:
• nutrient potentially affecting drug toxicity: Corticosteroids including Prednisone
chemistry/function:
• Dehydroepiandrosterone is a major adrenal hormone with no well accepted function.
• For many years researchers, uncertain as to the specific functions of DHEA, assumed that it was merely a buffer hormone, a reservoir upon which the adrenals could draw in order to produce other hormones. More recently researchers have discovered that cells contain specific DHEA receptor sites.
• Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined.
• Studies on animals and humans have suggested that DHEA-S has antiatherogenic effects. It has been hypothesized that insulin may have an atherogenic role and it has been reported recently that, surprisingly, DHEA-S levels decreased in normal men and women during the hyperinsulinemic-euglycemic technique.
dietary sources: Animal proteins are the richest dietary sources of DHEA.
forms:
• DHEA has usually been available as DHEA or in the DHEA-S forms.
• A synthetic form of DHEA is available as a supplement in tablet, capsule, liquid, and sublingual forms. The source material of either soy or wild yams is converted to DHEA in a laboratory.
• While some products have claimed to contain natural DHEA precursors from wild yam, no studies have ever confirmed that the body can convert any compounds in wild yam to DHEA or other steroid hormones .
• 3-Acetyl-7-Oxo DHEA (also known as 7-Keto DHEA) is a recently introduced an analog of DHEA which cannot be metabolized to active androgenic or estrogenic hormones but retains and enhances the immunologic, memory-enhancing and thermogenic effects of DHEA.
(Weeks C, et al. FASEB Jrnl, Abstracts Part II, 4428 (1998); Davidson MH, et al. FASEB Jrnl, Abstracts Part II, 4429 (1998)
deficiency:
• Aging: Overall, studies that have been conducted in humans show that DHEA treatment at dosages that restore serum levels may achieve normalization in some aging physiological systems and thereby indicate that DHEA deficiency may expedite the development of some diseases that are common in the elderly.
(Araneo B, et al. Ann N Y Acad Sci 1995;774:232-248; Morales AJ, et al. J Clin Endocrinol Metab 1994;78:1360-1367; Watson RR, et al. Drugs Aging 1996 Oct;9(4):274-91; Kalimi M, Regelson W. de Gruyter. New York. 1990. pp. 361-385; Yen SS, et al. Ann N Y Acad Sci 1995;774:128-142.)
• Depressed levels of DHEA have been reported in women with asthma, compared with matched controls.
(Weinstein RE, et al. J Allerg Clin Immol 1996;97:1-8.)
known or potential therapeutic uses: Adrenal insufficiency, AIDS/HIV, allergic disorders, Alzheimers disease, anti-aging/premature aging, autoimmune diseases, cancer, cardiovascular disease, chronic fatigue syndrome (CFS), depression, diabetes mellitus, enhancing immune response to viral and bacterial infections, hypercholesterolemia, impotence, menopause, multiple sclerosis, osteoporosis, obesity, rheumatoid arthritis, systemic lupus erythematosus (SLE).
mechanism: Stimulation and supplementation of adrenal hormone levels.
maintenance dose: Usually not necessary. Optimal levels of intake have not been established. Individuals who have not based diagnosed as having a hormonal deficiency pattern, preferably via lab tests, should usually not take DHEA as a supplement.
therapeutic dose:
• There is no consensus among practitioners who prescribe DHEA as to an optimal dose; some practitioners are routinely prescribing 50 mg per day for healthy men and 100 mg per day for healthy women, while others typically prescribe 2-30 mg per day. Much larger doses are being often given to patients with cancer, AIDS, and other serious conditions. Even when using lab testing to evaluate appropriateness of and response to DHEA, there are as yet no data on what constitutes an optimum serum level. Consequently. the judicious practice would be to err on the side of caution by using low doses of DHEA and observe discrimination in the use of supraphysiologic doses.
• One useful set of guidelines was provided by Alan Gaby, M.D., in Alternative Medicine Review, where he describes his usual practice of prescribing 5-15 mg/day for women and 10-30 mg/day for men. Many patients have obvious improvements with these doses. Higher doses may be appropriate, but in most cases, they are not necessary. However, individuals with lupus or other autoimmune diseases may need doses as high as 100 mg per day or more to obtain benefit.
(Gaby AR. Alt Med Rev. 1996:1(2);60-69.)
• Beyond those who prescribe DHEA, its supplementation is a controversial issue. Opinions vary widely as to the benefits and risks of using hormones, such as DHEA, as nutritional supplements. Any such usage should be monitored by a physician and is best undertaken after initially testing DHEA levels.
side effects:
• DHEA appears to be quite safe. Dosages as high as 1,600 mg/day have been given for periods of 28 days without any serious side effects, although mild abnormalities of blood sugar metabolism occurred in some cases. Minor side effects, such as acne or a slight increase in hair growth on the arms and legs, may occasionally occur when DHEA is taken.
• In one study of Lupus, utilizing 200 mg/day of DHEA orally for 3-6 months treatment, the only frequently noted side effect being mild acneiform dermatitis.
(Van Vollenhoven RF, et al. Arthritis Rheum 1994;37:1305-1310)
toxicity:
• For a steroid hormone, DHEA appears to be relatively safe. But, as with any hormonal supplementation, caution should be exercised in the use of DHEA as a supplement or therapeutic agent and use without the involvement of a nutritionally-trained healthcare professional is inadvisable. This is especially true when there is no data available on the effects of long-term administration of DHEA.
• Excessive levels of DHEA may be of particular concern to women due to their risk of inducing a variety of hormonal imbalances, including the potential effect of raising testosterone levels and possibly triggering male secondary sex characteristics at supplemental doses. One study found that a woman taking 100 mg of DHEA per day for one year started to develop facial hair, presumably as a consequence of. Some concerns have been raised that DHEA might contribute to liver damage or even liver cancer but no substantial confirmation of these harmful effects has been demonstrated.
(Casson PR, et al. Fertil Steril 1995;63:1027-1031.)
• In one study, the addition of 0.6% DHEA to the diet of rats reduced body weight and enhanced the development of chemically-induced pre-neoplastic pancreatic lesions. Although that dose of DHEA is extremely large (the equivalent human dose would be approximately 2.000 mg/day, this report indicates that DHEA is by no means innocuous and therefore it should be used with caution.
(Tagliaferro AR, et al. Adv Exp Med Biol 1992:322:119-129; Gaby AR. Alt Med Rev. 1996:1(2);67.)
• The possibilities presented by keto-7 DHEA may significantly reduce or eliminate many of the potential side effects and/or toxicities associated with use of DHEA.
contraindications:
• Some nutritional experts caution against anyone under 40 years of age using supplemental DHEA outside the supervision of an informed physician and primarily in the context of specifically-indicated health conditions.
(Murray M, Pizzorno J. 1998.)
• Personal or family history of hormone-related cancer, such as breast or prostate cancer. Given the role of DHEA as a precursor to both estrogen and testosterone, special caution should be exercised by individuals with a family history of hormone-related cancer. Some researchers have expressed concern that while younger women with breast cancer may have low levels of DHEA, postmenopausal women with breast cancer appear to have high levels of DHEA. (Zumoff B, et al. Canc Res 1981;41:3360-3363.)
• Kaposi's sarcoma: Caution may be appropriate given that high serum DHEA levels have been implicated in the pathogenesis of Kaposi's sarcoma in HIV/AIDS.
(Christieff N, et al. J Clin Pathology 1995: 48:513-518.)
• Initial indications are that keto-7 DHEA may significantly reduce or eliminate many of the potential side effects and/or toxicities associated with use of DHEA.