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ANTI-AGING DRUGS AND SUPPLEMENTS
 
 5.1 DRUGS THAT ARE HIGHLY RECOMMENDED (for inclusion in your supplementation anti-aging program) 
   
 
  DHEA  
   
Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension.
Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of youth".
DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.
DHEA: desire and resistance.
Association of DHEA-S and estradiol serum levels to symptoms of aging men.
DHEA treatment: myth or reality?
DHEA: an unknown star.
Uses of DHEA in aging and other disease states.
Dehydroepiandrosterone (DHEA)--youth hormone?
Dehydroepiandrosterone (DHEA)--structure, clinical importance and the role in human body.
DHEA(S): the fountain of youth.
The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging.
Dehydroepiandrosterone and diseases of aging.
Dehydroepiandrosterone (DHEA) treatment of depression.
DHEA-PC slows the progression of type 2 diabetes (non-insulin-dependent diabetes mellitus) in the ZDF/Gmi-fa/fa rat.
Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being.
 
 
   
   
Proc Natl Acad Sci U S A. 2003 Jul 23 [Epub ahead of print].
Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension.
Bonnet S, Dumas-De-La-Roque E, Begueret H, Marthan R, Fayon M, Santos PD, Savineau JP, Baulieu EE.
*Institut National de la Sante et de la Recherche Medicale, EMI 0356, Physiologie Cellulaire Respiratoire, Universite de Bordeaux II, 146, Rue Leo Saignat, 33076 Bordeaux Cedex, France; ()Institut National de la Sante et de la Recherche Medicale, U441, Atherosclerose, Avenue du Haut-Leveque, 33604 Pessac, France.

Pulmonary artery (PA) hypertension was studied in a chronic hypoxic-pulmonary hypertension model (7-21 days) in the rat. Increase in PA pressure (measured by catheterism), cardiac right ventricle hypertrophy (determined by echocardiography), and PA remodeling (evaluated by histology) were almost entirely prevented after oral dehydroepiandrosterone (DHEA) administration (30 mg/kg every alternate day). Furthermore, in hypertensive rats, oral administration, or intravascular injection (into the jugular vein) of DHEA rapidly decreased PA hypertension. In PA smooth muscle cells, DHEA reduced the level of intracellular calcium (measured by microspectrofluorimetry). The effect of DHEA appears to involve a large conductance Ca(2+)-activated potassium channel (BKCa)-dependent stimulatory mechanism, at both function and expression levels (isometric contraction and Western blot), via a redox-dependent pathway. Voltage-gated potassium (Kv) channels also may be involved because the antagonist 4-amino-pyridine blocked part of the DHEA effect. The possible pathophysiological and therapeutic significance of the results is discussed.

   
   
CNS Drug Rev. 2003 Spring;9(1):21-40.
Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of youth".
Racchi M, Balduzzi C, Corsini E.
Department of Experimental and Applied Pharmacology, University of Pavia, Italy.

The physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The major interest in DHEA derives from its unique pattern of activity. Its levels exhibit a dramatic age-related decline that supports significant involvement of DHEA(S) in the aging process. Particularly relevant to the aging process is the functional decline that involves memory and cognitive abilities. DHEA is derived mainly from synthesis in the adrenal glands and gonads. It can also be detected in the brain where it is derived from a synthesis that is independent from peripheral steroid sources. For this reason DHEA and other steroid molecules have been named "neurosteroids." Pharmacological studies on animals provided evidence that neurosteroids could be involved in learning and memory processes because they can display memory-enhancing properties in aged rodents. However, human studies have reported contradictory results that so far do not directly support the use of DHEA in aging-related conditions. As such, it is important to remember that plasma levels of DHEA(S) may not reflect levels in the central nervous system (CNS), due to intrinsic ability of the brain to produce neurosteroids. Thus, the importance of neurosteroids in the memory process and in age-related cognitive impairment should not be dismissed. Furthermore, the fact that the compound is sold in most countries as a health food supplement is hampering the rigorous scientific evaluation of its potential. We will describe the effect of neurosteroids, in particular DHEA, on neurochemical mechanism involved in memory and learning. We will focus on a novel effect on a signal transduction mechanism involving a classical "cognitive kinase" such as protein kinase C. The final objective is to provide additional tools to understand the physiological role and therapeutic potentials of neurosteroids in normal and/or pathological aging, such as Alzheimer's disease.

   
   
Neurology. 2003 Apr 8;60(7):1071-6.
DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.
Wolkowitz OM, Kramer JH, Reus VI, Costa MM, Yaffe K, Walton P, Raskind M, Peskind E, Newhouse P, Sack D, De Souza E, Sadowsky C, Roberts E; DHEA-Alzheimer's Disease Collaborative Research.
Department of Psychiatry, Center for Neurobiology and Psychiatry, University of California San Francisco (UCSF) School of Medicine, USA.

OBJECTIVE: To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD. METHOD: Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint. RESULTS: Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points. CONCLUSIONS: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.

   
   

Gynecol Obstet Fertil. 2002 Dec;30(12):961-9.
DHEA: desire and resistance.
Belaisch J.

DHEA is a prohormone that is secreted by the corticoadrenal glands on a nyctohemeral rhythm alike to that of testosterone. Its plasmatic level gets reduced with ageing in a great amount of individuals, but not in all. Moreover, DHEA is a neurosteroid synthesized by certain neurons. As shown by correlation studies, lowered levels of DHEA wre linked to a higher death rate, in part of the studied population. Besides, an improvement in well being as well as in some mental functions, after a 50 mg daily intake, was shown in preliminary studies. Many well-conducted studies followed which only partially confirmed the previous ones. Nowadays, it seems to be taken for granted that DHEA becomes Estrogens and androgens and that its action on women is mainly an androgenic one. DHEA becomes active after intracellular transformation, which varies according to the enzymatic set of cells. Some effect on elderly women's libido, and improvement in erectile dysfunction in men without vascular pathology but a lowered DHEA level, has been observed. Thus, using DHEA in order to cure sexual troubles might be considered, although the possible negative effects of DHEA, especially on breast and prostate, have not been discarded yet. The conditions under which it could have a beneficial effect on mental functions remains to be discovered. Acknowledgement of those pathological situations, in which DHEA could prove useful, as well as the administration posology is, therefore, crucial.

   
   
Aging Male. 2002 Dec;5(4):233-8.
Association of DHEA-S and estradiol serum levels to symptoms of aging men.
Ponholzer A, Plas E, Schatzl G, Jungwirth A, Madersbacher S; Austrian Society of Urology.
Department of Urology and Andrology and Ludwig Boltzmann Institute for Urological Oncology, Danube Hospital, Langobardenstrasse 122, 1220 Vienna, Austria.

OBJECTIVES: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. METHODS: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. RESULTS: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. CONCLUSION: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.

   
   
Trends Endocrinol Metab. 2002 Sep;13(7):288-94.
DHEA treatment: myth or reality?
Allolio B, Arlt W.
Dept Medicine, Endocrine and Diabetes Unit, University of Wurzburg, Josef-Schneider-Str. 2, 97080 Wurzburg, Germany.

Dehydroepiandrosterone (DHEA) and its sulfate ester are major secretory products of the human adrenal. Serum DHEA concentrations decline with advancing age and DHEA supplementation in elderly people has been advertized as anti-aging medication. However, such claims are based on experiments in rodents with a fundamentally different DHEA physiology. In humans, DHEA is a crucial precursor of sex steroid biosynthesis and exerts indirect endocrine and intracrine actions following conversion to androgens and Estrogens. In addition, it acts as a neurosteroid via effects on neurotransmitter receptors in the brain. DHEA has considerable effects on mood, well-being and sexuality in patients with adrenal insufficiency, and also in those with mood disorders. However, subjects with a physiological, age-related decline in DHEA secretion show little benefit from DHEA administration. Future research should focus on DHEA treatment for adrenal insufficiency, and DHEA administration in both patients receiving chronic glucocorticoid treatment and women with androgen deficiency.

   
   
Rev Med Interne. 2002 May;23(5):436-46.
DHEA: an unknown star.
Schlienger JL, Perrin AE, Goichot B.
Service de medecine interne et nutrition, hopital de Hautepierre, 67098 Strasbourg, France.

PURPOSE: To clarify the physiological function of dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, which remains poorly understood. To analyse the beneficial effects of a supplementation in order to alleviate its decrease in ageing and improve well-being. CURRENT KNOWLEDGE AND KEY POINTS: DHEA (and its sulfate) acts on peripheral tissues as an androgenic and estrogenic precursor. It is also considered as a neurosteroid. DHEA administration in several pathological animal models is promising, especially in metabolic diseases such as obesity and insulin resistance. It appears like a factor of immunomodulation and facilitates cognitive acquisition. In humans there is little evidence that DHEA may be useful in characterized pathologies apart from adrenal insufficiency. An interesting effect was also noted in severe systemic lupus erythematosus. The effects on cognitive and neuropsychiatric diseases such as midlife dysthymia are not yet convincing. Prospective studies of supplementation versus placebo indicate inconstant improvement in well-being in the post-menopausal state. DHEA is not a panacea against ageing despite there being a well-established aging-related decrease of DHEA. Contrary to some assertions there are no proven relations between cardiovascular or cancer risk. FUTURE PROSPECTS AND PROJECTS: Until now adrenal insufficiency has been the only well-documented indication of an oral DHEA supplementation. However, DHEA may be a good way for androgen supplementation in menopausal men. Further investigations are needed to better know the anti-inflammatory and immunomodulation properties of DHEA. At the least, prospective studies on large populations are necessary to assess the true benefits and dangers of DHEA in prevention of ageing.

   
   
Ageing Res Rev. 2002 Feb;1(1):29-41.
Uses of DHEA in aging and other disease states.
Johnson MD, Bebb RA, Sirrs SM.
Division of Endocrinology, University of British Columbia, 262-575 West 8th Avenue, Vancouver BC, Canada V5Z 1C6.

Dehydro-3-epiandrosterone is a steroid hormone synthesized in large quantities by the adrenal gland whose physiologic role remains unclear. The effects of DHEA could be estrogenic or androgenic, depending on the hormonal milieu. Low levels of DHEA are associated with aging, cardiovascular disease in men, and an increased risk of pre-menopausal breast and ovarian cancer. High levels of DHEA might increase the risk of postmenopausal breast cancer. Therapeutically DHEA might be useful for improving psychological well-being in the elderly, reducing disease activity in people with mild to moderate systemic lupus erythematosus and myotonic dystrophy, improving mood in those clinically depressed, and improving various parameters in women with adrenal insufficiency. Although many other claims have been made for DHEA in diverse conditions, such as aging, dementia, and AIDS, no well-designed clinical trials have clearly substantiated the utility and safety of long-term DHEA supplementation.

   
   
Wiad Lek. 2001;54(11-12):693-704.
Dehydroepiandrosterone (DHEA)--youth hormone?
Zdrojewicz Z, Kesik S.
Katedry i Kliniki Endokrynologii i Diabetologii Akademii Medycznej we Wroclawiu.

Dehydroepiandrosterone (DHEA) and its sulphated metabolite (DHEA-S) are endogenous steroid hormones, synthesized by the adrenal cortex, gonads and CNS. The secretion profile changes with age and depends on the sex. Human DHEA and DHEA-S levels decline linearly and systematically with age and suggest the potential importance of that parameter as a biomarker of ageing. The counteraction of DHEA against atherosclerotic disease, cancer growth, diabetes mellitus, insulin resistance, obesity and the influence on immunological functions are observed in researches. DHEA influences the condition of mind, cognition functions, memory and well-being. DHEA hormonal replacement therapy is expected to lengthen human life by the stoppage of physiological degeneration changes and prevention of age-related clinical disorders.

   
   
Postepy Hig Med Dosw. 2001;55(6):835-54.
Dehydroepiandrosterone (DHEA)--structure, clinical importance and the role in human body.
Zdrojewicz Z, Ciszko B.
Katedra i Klinika Endokrynologii i Diabetologii Akademii Medycznej we Wroclawiu.

DHEA and DHEA-S are hormones synthetized primarily by the adrenal cortex. The levels oh this hormones are systematically decreased, beginning from the fourth life decade. The levels of this hormones are also abberrated as a consequence of divorce systematical diseases like cardiovascular diseases, skeletal diseases, diabetes mellitus or obesity. This hormones, probably, have antiaheromatic facilities. There are also data suggesting their influence on stimulation of immunological system. It is already confirmed that the levels of this hormones are modified in congenital function disorders that are present in different diseases, like Alzheimer diseases, and oral administration of DHEA can improves the memory. Presumably DHEA-S have also anticarcinogenic facilities. The levels of this hormones can be also a marker monitoring the course of pregnancy. There are still a lot of discrepancies between results of different studies and it is very difficult to describe their role in human body. Because their levels are decreased with ageing process, this observation makes the researchers call them as the "youth hormones".

   
   
J Med Assoc Thai. 2001 Oct;84 Suppl 2:S605-12.
DHEA(S): the fountain of youth.
Leowattana W.
Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are weak androgens produced primarily by the adrenal gland. Although their plasma concentrations by far exceed those of any other adrenal product, their physiological roles have not yet been determined. In plasma, where the major portion of these hormones is present in the sulfate form, it is possible that DHEAS serves as a reservoir for DHEA. Since various tissues have been shown to contain steroid sulfatases. The peak plasma levels of DHEA and DHEAS occur at approximately age 25 years, decrease progressively thereafter, and diminish by 95 per cent around the age of 85 years. The decline of DHEAS concentrations with aging has led to the suggestion that DHEAS could play a role in itself and be implicated in longevity. Moreover, the epidemiological evidence has shown that adult men with high plasma DHEAS levels are less likely to die of cardiovascular disease. DHEA has also been shown to increase the body's ability to transform food into energy and burn off excess fat. Another recent finding involves the anti-inflammatory properties of DHEA. It has been known that DHEA can lower the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). It should be pointed out that chronic inflammation is known to play a critical role in the development of the killer diseases of aging: heart disease, Alzheimer's disease and certain types of cancer. In conclusion, DHEA or DHEAS administration combined with conventional treatment may be implicated in particular conditions to improve the quality of life.

   
   
Lipids. 2000 Mar;35(3):325-31.
The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging.
Williams JR.
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA.

With the passage of the U.S. Dietary Supplement Health and Education Act of 1994, dehydroepiandrosterone (DHEA, 5-androsten-3beta-ol-17-one) has become widely available, and a large and growing market has developed for this "fountain of youth." DHEA has been shown to have significant beneficial effects in animals, which may lead to clinical uses in man. Historically, the U.S. Food and Drug Administration removed DHEA from the over-the-counter market in 1985 because there was no support for the health claims that were made for this product. Almost all of the biological data was on animals and there was a lack of demonstrated efficacy in humans. Recently there have been a number of small clinical trials in humans but the results have not been as positive as in the animal tests. This review will be restricted to the effects of DHEA on carcinogenesis, obesity, the immune system, and aging. Four hypotheses have been proposed to explain the underlying biochemical mechanism(s) by which DHEA exerts its beneficial properties. The first is based on the inhibitory effect of DHEA on mammalian glucose-6-phosphate dehydrogenase. This mechanism can explain the antiinitiation and antipromotion steps in some cases of carcinogenesis. The second biochemical mechanism involves the induction of peroxisomes and peroxisome-associated enzymes. The third explanation is that DHEA works in a similar fashion to the known anticarcinogenic action of food restriction. An antiglucocorticoid mechanism has also been suggested. A hypothesis for the increase followed by the decrease in the levels of DHEA with age is proposed. A number of new synthetic DHEA analogs have been synthesized and tested. They offer the best hope for the development of a clinically useful drug based on the properties of DHEA.

   
   
Drugs Aging. 1996 Oct;9(4):274-91.
Dehydroepiandrosterone and diseases of aging.
Watson RR, Huls A, Araghinikuam M, Chung S.
Arizona Prevention Center, University of Arizona, School of Medicine, Tucson, USA.

Dehydroepiandrosterone (DHEA; prasterone) is a major adrenal hormone with no well accepted function. In both animals and humans, low DHEA levels occur with the development of a number of the problems of aging: immunosenesence, increased mortality, increased incidence of several cancers, loss of sleep, decreased feelings of well-being, osteoporosis and atherosclerosis. DHEA replacement in aged mice significantly normalised immunosenescence, suggesting that this hormone plays a key role in aging and immune regulation in mice. Similarly, osteoclasts and lymphoid cells were stimulated by DHEA replacement, an effect that may delay osteoporosis. Recent studies do not support the original suggestion that low serum DHEA levels are associated with Alzheimer's disease and other forms of cognitive dysfunction in the elderly. As DHEA modulates energy metabolism, low levels should affect lipogenesis and gluconeogenesis, increasing the risk of diabetes mellitus and heart disease. Most of the effects of DHEA replacement have been extrapolated from epidemiological or animal model studies, and need to be tested in human trials. Studies that have been conducted in humans show essentially no toxicity of DHEA treatment at dosages that restore serum levels, with evidence of normalisation in some aging physiological systems. Thus, DHEA deficiency may expedite the development of some diseases that are common in the elderly.

   
   
Biol Psychiatry. 1997 Feb 1;41(3):311-8.
Dehydroepiandrosterone (DHEA) treatment of depression.
Wolkowitz OM, Reus VI, Roberts E, Manfredi F, Chan T, Raum WJ, Ormiston S, Johnson R, Canick J, Brizendine L, Weingartner H.
Department of Psychiatry, University of California, San Francisco, School of Medicine 94143-0984, USA.

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

   
   
Diabetes Technol Ther. 2001 Summer;3(2):211-9.
DHEA-PC slows the progression of type 2 diabetes (non-insulin-dependent diabetes mellitus) in the ZDF/Gmi-fa/fa rat.
Byrne JJ, Bradlow HL.
Supergen, Inc., Dublin, California, USA.

The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is complex and development is manifested by initial insulin resistance coupled with elevated insulin levels in the early diabetic state with concomitant increases in circulating levels of glucose and triglycerides. This is followed by a decline in insulin levels due to pancreatic exhaustion. Our results show that administration of DHEA-PC, a phosphocholine conjugate of dehydroepiandrosterone (DHEA), delayed the development of NIDDM symptoms and the onset of type 2 diabetes in the ZDF/Gmi-fa/fa rat model. The treatment consisted of weekly implantation of subdermal osmotic infusion pumps in the rats starting at 6 weeks of age (n = 5 animals per group). For the first three weeks the pumps delivered 6 mg/day/rat followed by 12 mg/day/rat for 1 week (control group pumps delivered only carrier vehicle) after which the pumps were removed. Plasma was collected weekly from day 0 through day 58, and glucose, triglycerides, cholesterol, insulin, IGF-1, and IGF-BP3 levels were measured. Data were analyzed by two-way ANOVA. Following 3 weeks of treatment with DHEA-PC, plasma glucose levels in the treated group remained low, 150+/-9 mg/dL, while the levels in the control animals steadily increased to 320+/-100 mg/dL (p < 0.05). After the DHEA-PC treatment ended, plasma glucose plateaued for 10 days and then took 25 days to reach the level in the control animals (p < 0.05). After 2 weeks of DHEA-PC treatment, plasma triglyceride levels in the treated group remained low, 85+/-24 mg/dL, while the level in the control rats increased to 180+/-35 mg/dL (p < 0.05). After the treatment was terminated triglyceride levels in the treated group increased to control levels within 2 days. Insulin, IGF-1, IGF-BP3, cholesterol, body weight, and food consumption were not changed by DHEA-PC treatment (p < 0.05). Therefore, the delay of increases in plasma glucose and triglycerides, caused by DHEA-PC, was not the result of differences in caloric intake, increased insulin, or increased IGF-1 levels. The data suggest that DHEA-PC delayed the onset of the two most important parameters of NIDDM, namely hyperglycemia and hypertriglyceridemia.

   
   
Cochrane Database Syst Rev. 2000;(2):CD000304.
Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being.
Huppert FA, Van Niekerk JK, Herbert J.
Department of Psychiatry, Cambridge University, Box 189 Addenbrooke's Hospital, Cambridge, UK, CB2 2QQ.

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS in aging and dementia, we believe it is timely to undertake a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans, in large-scale and properly controlled trials, which would evaluate effective dosage, acceptable route and duration of administration and side effect profiles. This is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves psychological well-being and/or improves cognitive function or reduces the rate of decline of cognitive function in older adults or in individuals with dementia. SEARCH STRATEGY: All available electronic databases, hand searched journals, personal communications and conference abstracts were searched for randomised controlled trials of DHEA in well-being and cognition. The total yield from searching was 415 and the detailed breakdown is given in the body of this review. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA or DHEAS were considered for inclusion in the review. Studies where groups are matched, rather than randomised, were also considered. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. Where possible and appropriate, data were pooled and the mean differences estimated. MAIN RESULTS: The published DHEA trials fall into 2 categories: 1. four German studies in which DHEA was administered for a period of two weeks or less; 2. a USA study in which DHEA was administered for three months. Well-being was assessed in both sets of studies and a significant improvement was reported in the longer duration USA study, while no effect was reported in the shorter duration studies. The USA study used an open-ended questionnaire for self-assessment of well-being and stated that 67% of men and 82% of women reported enhanced well-being on DHEA compared with placebo. There was no significant change on an analogue measure of libido. The German studies assessed mood and well-being with a number of standardised scales and reported no significant effects of DHEA on any of them. Only the German studies examined performance on cognitive tests, i.e. memory, verbal fluency, speed of processing, etc. They reported no significant benefit of DHEA. REVIEWER'S CONCLUSIONS: The data at present offer limited support for improvement in a sense of well-being following DHEA treatment. This effect was reported only in the longer-term study which used a crude measure of well-being. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment, although cognitive function was only measured in the short-duration trials. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, it is clear that high-quality trials need to be undertaken in older adults, in which (a) the duration of DHEA treatment is in excess of two weeks, (b) the number of participants is large enough to detect effects if they exist, and (c) the outcome measures include validated scales for assessment of mood and well-being, and objective tests of cognitive function. Recently, studies of DHEA supplementation in clinical depression and Alzheimer's Disease have been completed in the USA. As soon as the results are available these studies will be reviewed. Currently, two trials (in France and the USA) in normal elderly are in progress.

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FASTING / LOW CALORIE PROGRAMS
on the Adriatic Coast
The Anti-Aging Fasting Program consists of a 7-28 days program (including 3 - 14 fasting days). 7-28-day low-calorie diet program is also available .
More information
    The anti-aging story (summary)
Introduction. Statistical review. Your personal aging curve
  Aging and Anti-aging. Why do we age?
    2.1  Aging forces (forces that cause aging
     
Internal (free radicals, glycosylation, chelation etc.) 
External (Unhealthy diet, lifestyle, wrong habits, environmental pollution, stress, poverty-change "poverty zones", or take it easy. etc.) 
    2.2 Anti-aging forces
     
Internal (apoptosis, boosting your immune system, DNA repair, longevity genes) 
External (wellness, changing your environment; achieving comfortable social atmosphere in your life, regular intake of anti-aging drugs, use of replacement organs, high-tech medicine, exercise)
    2.3 Aging versus anti-aging: how to tip the balance in your favour!
 
    3.1 Caloric restriction and fasting extend lifespan and decrease all-cause mortality (Evidence)
      Human studies
Monkey studies
Mouse and rat studies
Other animal studies
    3.2 Fasting and caloric restriction prevent and cure diseases (Evidence)
        Obesity
Diabetes
Hypertension and Stroke
Skin disorders
Mental disorders
Neurogical disorders
Asthmatic bronchitis, Bronchial asthma
Bones (osteoporosis) and fasting
Arteriosclerosis and Heart Disease
Cancer and caloric restriction
Cancer and fasting - a matter of controversy
Eye diseases
Chronic fatigue syndrome
Sleeping disorders
Allergies
Rheumatoid arthritis
Gastrointestinal diseases
Infertility
Presbyacusis
    3.3 Fasting and caloric restriction produce various
      biological effects. Effects on:
        Energy metabolism
Lipids metabolism
Protein metabolism and protein quality
Neuroendocrine and hormonal system
Immune system
Physiological functions
Reproductive function
Radio-sensitivity
Apoptosis
Cognitive and behavioral functions
Biomarkers of aging
    3.4 Mechanisms: how does calorie restriction retard aging and boost health?
        Diminishing of aging forces
  Lowering of the rate of gene damage
  Reduction of free-radical production
  Reduction of metabolic rate (i.e. rate of aging)
  Lowering of body temperature
  Lowering of protein glycation
Increase of anti-aging forces
  Enhancement of gene reparation
  Enhancement of free radical neutralisation
  Enhancement of protein turnover (protein regeneration)
  Enhancement of immune response
  Activation of mono-oxygenase systems
  Enhance elimination of damaged cells
  Optimisation of neuroendocrine functions
    3.5 Practical implementation: your anti-aging dieting
        Fasting period.
Re-feeding period.
Safety of fasting and low-calorie dieting. Precautions.
      3.6 What can help you make the transition to the low-calorie life style?
        Social, psychological and religious support - crucial factors for a successful transition.
Drugs to ease the transition to caloric restriction and to overcome food cravings (use of adaptogenic herbs)
Food composition
Finding the right physician
    3.7Fasting centers and fasting programs.
  Food to eat. Dishes and menus.
    What to eat on non-fasting days. Dishes and menus. Healthy nutrition. Relation between foodstuffs and diseases. Functional foods. Glycemic index. Diet plan: practical summary. "Dr. Atkins", "Hollywood" and other fad diets versus medical science
     

Vegetables
Fruits
Bread, cereals, pasta, fiber
Glycemic index
Fish
Meat and poultry
Sugar and sweet
Legumes
Fats and oils
Dairy and eggs
Mushrooms
Nuts and seeds
Alcohol
Coffee
Water
Food composition

  Anti-aging drugs and supplements
    5.1 Drugs that are highly recommended
      (for inclusion in your supplementation anti-aging program)
        Vitamin E
Vitamin C
Co-enzyme Q10
Lipoic acid
Folic acid
Selenium
Flavonoids, carotenes
DHEA
Vitamin B
Carnitin
SAM
Vinpocetine (Cavinton)
Deprenyl (Eldepryl)
    5.2 Drugs with controversial or unproven anti-aging effect, or awaiting other evaluation (side-effects)
        Phyto-medicines, Herbs
HGH
Gerovital
Melatonin
      5.3 Drugs for treatment and prevention of specific diseases of aging. High-tech modern pharmacology.
        Alzheimer's disease and Dementia
Arthritis
Cancer
Depression
Diabetes
Hyperlipidemia
Hypertension
Immune decline
Infections, bacterial
Infections, fungal
Memory loss
Menopause
Muscle weakness
Osteoporosis
Parkinson's disease
Prostate hyperplasia
Sexual disorders
Stroke risk
Weight gaining
    5.4 The place of anti-aging drugs in the whole
      program - a realistic evaluation
 
    6.1 Early diagnosis of disease - key factor to successful treatment.
      Alzheimer's disease and Dementia
Arthritis
Cancer
Depression
Diabetes
Cataracts and Glaucoma
Genetic disorders
Heart attacks
Hyperlipidemia
Hypertension
Immune decline
Infectious diseases
Memory loss
Muscle weakness
Osteoporosis
Parkinson's disease
Prostate hyperplasia
Stroke risk
Weight gaining
    6.2 Biomarkers of aging and specific diseases
    6.3 Stem cell therapy and therapeutic cloning
    6.4 Gene manipulation
    6.5 Prosthetic body-parts, artificial organs
        Blood
Bones, limbs, joints etc.
Brain
Heart & heart devices
Kidney
Liver
Lung
Pancreas
Spleen
    6.6 Obesity reduction by ultrasonic treatment
  Physical activity and aging. Experimental and clinical data.
        Aerobic exercises
Stretching
Weight-lifting - body-building
Professional sport: negative aspects
 
  Conclusion: the whole anti-aging program
    9.1 Modifying your personal aging curve
      Average life span increment. Expert evaluation.
     
Periodic fasting and caloric restriction can add 40 - 50 years to your lifespan
Regular intake of anti-aging drugs can add 20-30 years to your lifespan
Good nutrition (well balanced, healthy food, individually tailord diet) can add 15-25 years to your lifespan
High-tech bio-medicine service can add 15-25 years to your lifespan
Quality of life (prosperity, relaxation, regular vocations) can add 15-25 years to your lifespan
Regular exercise and moderate physical activity can add 10-20 years to your lifespan
These approaches taken together can add 60-80 years to your lifespan, if you start young (say at age 20). But even if you only start later (say at 45-50), you can still gain 30-40 years


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    9.2 The whole anti-aging life style - brief summary 
    References eXTReMe Tracker
        The whole anti-aging program: overview
         
       

       
     
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