DHEA – the hormone

REDUCES INFLAMMATION, ENHANCES IMMUNITY, PROTECTS ARTERIES AND THE BRAIN – by Ivy Greenwell – extract from Life Extension magazine
Dehydroepiandrosterone (DHEA) hormones are the most abundant steroids in the human body. Low levels of DHEA are associated with aging and disease states. Specifically, a deficiency of DHEA has been found to correlate with immune dysfunction, inflammation, greater risk of certain cancers, heart disease in men, and osteoporosis. The special interest in DHEA replacement, however, stems from its function as a prohormone, meaning a precursor to a great variety of beneficial steroids, both in the estrogenic and androgenic family, on an “as-needed” basis.
Perhaps the most exciting new finding relates to the antiatherogenic benefits of DHEA. The dramatic aging-related drop in DHEA levels is accompanied by an equally dramatic rise in cardiovascular disease. We have now come closer to elucidating the cardioprotective mechanism of DHEA. It appears that DHEA is incorporated into both high and low-density cholesterol, protecting it from oxidation. In the aged, however, cholesterol-bound DHEA becomes virtually undetectable, and the cholesterol molecules are much more susceptible to oxidation than in young individuals. But this is not the end of the story. It turns out that DHEA also increases the activity of platelet superoxide dismutase (SOD), one of our most important antioxidant enzymes. Thus, DHEA seems to play an essential role as part of the body’s antioxidant defenses.
Another recent finding involves the anti-inflammatory properties of DHEA. It has been known for a long time that DHEA can lower the levels of interleukin-6 (IL-6), a pro-inflammatory cytokine (meaning a chemical messenger used by the immune system) that seriously escalates the inflammatory process, recruiting immune cells that often end up destroying healthy tissue as well. Now it has been established that DHEA can lower the production of another inflammatory cytokine as well, one called tumor necrosis factor alpha (TNF-alpha). The levels of both IL-6 and TNF-alpha rise with aging, showing an increased inflammatory state and possible immune dysfunction. The role of DHEA in regulating the immune response has been shown to include also the enhanced secretion of interferon-gamma. The decline in DHEA levels is closely tied to immunosenescence.
This is excellent news for those who suffer from chronic inflammatory diseases. However, it could be argued that aging itself is, in a sense, a chronic inflammatory state. The levels of various chemical mediators of inflammation, such as IL-6 and TNF, increase as we age. At the same time, our production of DHEA plummets with aging. Maintaining youthful levels of DHEA means less chronic inflammation. 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.
One surprising finding showed that DHEA can help some infertile patients ovulate and become pregnant, making previously ineffective ovarian stimulation succeed at last.
More good news includes also the finding that DHEA protects brain tissue under conditions simulating stroke and trauma damage, and is likely to be involved in protecting the brain against the development of Alzheimer’s disease. The neuroprotective mechanism of DHEA appears to go beyond its anti-glucocorticoid effect, that is, its ability to antagonize the harmful effects of cortisol; anti-inflammatory action is likely to be involved as well. DHEA has also been shown to lower hyperglycemia (elevated blood sugar) in diabetic rats, and protect their kidneys from the damage caused by high blood sugar. In addition, DHEA enhances the immune response and helps us fight infection; several studies have confirmed its usefulness in combating bacterial, parasitic and viral infections, including HIV. DHEA also helps protect the thymus against cortisol-induced atrophy.
Speaking of cortisol, we are beginning to understand that it is the ratio of DHEA to cortisol that is of critical importance in aging and certain diseases such as AIDS. A recent French study done at the Pasteur Institute in Paris found that the minority of patients who do not succumb to the severe side effects of highly aggressive antiretroviral therapy show a normalized DHEA/cortisol ratio. The majority of AIDS patients, however, have an abnormally low DHEA/cortisol ratio and thus suffer from symptoms usually associated with excess cortisol, even though their cortisol levels are within normal. Cardiac patients and the victims of Alzheimer’s disease also show low DHEA/cortisol ratio. The manipulation of this crucial ratio, including DHEA therapy, could prove highly significant both in the treatment of AIDS and in anti-aging medicine in general. In fact, a small pilot study has already indicated that DHEA combined with an anti-inflammatory drug such as indomethacin can moderate or even normalize the various pathological changes of AIDS-related lipodystrophy.
One surprising finding showed that an 80 mg/day dose of DHEA can help some infertile patients ovulate and become pregnant, making previously ineffective ovarian stimulation succeed at last (in one case, the result was twins!). An animal study confirmed that DHEA is important as a steroidogenic substrate (precursor of other hormones) in ovarian production of various sex steroids. Interestingly, immunomodulatory 7-hydroxy metabolites of DHEA have also been discovered in human semen, with possible further implications for fertility. In postmenopausal women, research on DHEA replacement continues to indicate improved well-being and libido, among many other benefits. We are also closer to understanding the mechanism through which DHEA enhances the sense of well-being: it significantly increases the levels of beta-endorphins.
Those readers who are considering following a ketogenic (low-carbohydrate) diet may be interested in a small study done on rheumatoid arthritis patients: the low-calorie ketogenic diet using less than 40 g of carbohydrates per day resulted in a 34% rise in DHEA within a week; the ketogenic diet was as effective as sub-total fast in raising DHEA levels. This study needs to be replicated, however, using a larger number of healthy subjects. In primates, calorie restriction has indeed been found to preserve higher DHEA levels, indicating a slower rate of aging. In humans, fasting is known to raise DHEA levels in both sexes. Anorexic and bulimic women likewise show higher serum DHEA. Exercise can also raise DHEA in some individuals, possibly due to the inverse relationship between DHEA and insulin. Finally, while meditation has long been known to increase DHEA, participation in drum circles has also been shown to increase DHEA and DHEA/cortisol ratio, confirming the hypothesis that stress reduction in general boosts DHEA production, probably through a shift of adrenal steroidogenesis from cortisol to DHEA. High insulin, high cortisol and low DHEA constitute a large part of the pathological endocrine profile of aging. Restoring the correct hormonal ratios should be one of the primary goals of any anti-aging program.
DHEA protects the cardiovascular system
Epidemiological studies continue to confirm the correlation between the levels of DHEA in men with their risk of cardiovascular disease. Most recently, the Massachusetts Male Aging Study followed over 1700 men between the ages of 40 and 70 for nine years. The authors found that men in the lowest quartile of serum DHEA at baseline were 60% more likely to develop ischemic heart disease. Low serum DHEA was also a significant predictor. Likewise, studies continue to confirm lower DHEA values in cardiac patients combined with higher insulin levels, wi
th a “close inverse correlation” between insulin and DHEA. This raises the question as to whether DHEA is the “missing link” in hyperinsulinemia and atherosclerosis.
A very important Canadian study has partly elucidated the way DHEA works to protect blood vessels against atherosclerosis. The authors found that in elderly patients vitamin E is unable to restore the resistance of LDL to oxidation back to the levels found in youth. DHEA, on the other hand, did increase the resistance of LDL to oxidation in a dose-dependent manner. This study found evidence indicating that DHEA is actually incorporated into the molecules of both LDL and HDL cholesterol, and acts as an antioxidant. During aging, however, cholesterol-bound DHEA practically disappears. In the elderly, the levels of cholesterol-bound DHEA are virtually nondetectable, and their LDL cholesterol becomes very susceptible to oxidative damage. (Estrogen esters apparently function in a similar way, protecting LDL against oxidation.)
DHEA has also been shown to reduce the amount of atherosclerotic plaque in rabbits fed a high-cholesterol diet. One clue about the cardioprotective mechanism of DHEA comes from a recent Japanese study, which compared animals given DHEA with animals given DHEA together with an aromatase inhibitor, a compound that prevents the conversion of DHEA to estrogens. The amount of the plaque was diminished by 60% in animals receiving DHEA alone, but only by 30% in animals receiving DHEA and an aromatase inhibitor. The authors conclude that approximately half of the antiatherosclerotic effect of DHEA is due to its conversion to estrogens and an increased release of nitric oxide.
Another study using male castrated cholesterol-fed rabbits as an animal model of atherosclerosis compared the effects of oral DHEA against those of testosterone enanthate given by injection, oral synthetic testosterone and placebo. Sham-operated non-castrated rabbits also served as a control group. Aortic atherosclerosis was highest in the placebo group and lowest in the group receiving testosterone injections. The degree of atherosclerosis was intermediate in the DHEA group, which did better than the oral testosterone group, and slightly better than the noncastrated rabbits that had the benefit of their own testosterone. The study showed that both testosterone and DHEA help prevent atherosclerosis. The benefit could be only partly explained in terms of the impact on the serum lipids.
Finally, a study done at the University of Wroclaw, Poland, found that DHEA decreased the levels of serum lipid peroxides in rabbits fed a normal diet, but not in rabbits with induced severe hypercholesterolemia. However, both healthy rabbits and rabbits with extremely high cholesterol showed an increase in the activity of platelet superoxide dismutase (SOD), a crucial antioxidant enzyme. Again, it should be stressed that this increase in SOD activity was observed both in rabbits fed a normal diet and in rabbits fed an atherogenic diet, which usually show decreased SOD activity. Increase in SOD activity may partly explain DHEA’s antioxidant effects.
Overall, there seems to be a consensus that while DHEA may not be cardioprotective in women, men with low levels of DHEA are at a greater risk of a heart attack. For older men, cardiovascular health appears to be yet another excellent reason for taking DHEA supplements.
Brain protection
DHEA is especially abundant in the human brain. Many earlier studies reported a protective effect of DHEA against the deterioration of mental function with aging, and an inverse correlation between DHEA levels and neurodegerative disease such as Alzheimer’s. A recent Canadian study found that rats implanted with a high dose of DHEA showed significantly less hippocampal damage after stroke was induced (60% injured neurons as compared to 88% for placebo).
In another study, DHEA proved to be the most potent of all the steroids tested in its ability to inhibit the formation of excess reactive astroglia in the event of a penetrating wound of the cerebral cortex, thus downregulating the immune response, which otherwise might injure healthy neurons in the vicinity of the wound. It has been demonstrated that DHEA markedly inhibits tumor necrosis factor alpha (TNF-alpha) and IL-6 in glial cells. The ability to lower the levels of these inflammatory mediators may be an important part of the neuroprotective mechanism of DHEA.
In addition, DHEA has been shown to protect against the toxicity of the amyloid-beta protein and excess glutamate. Treatment with glutamate produced a copious increase in the neuronal glucocorticoid receptor. Treatment with DHEA reversed this increase, demonstrating again the anti-glucocorticoid action of DHEA.
DHEA is often advertised as a remedy for depression. At this point we know that depression is more than just a shortage of neurotransmitters; it is a whole-body degenerative disease, the most frightening aspect of which is aging-like loss of neural tissue.
DHEA is often advertised as a remedy for depression. At this point we know that depression is more than just a shortage of neurotransmitters; it is a whole-body degenerative disease, the most frightening aspect of which is aging-like loss of neural tissue. There has been a steady interest in DHEA as an antidepressant. First, however, it should be established whether depression is indeed associated with low DHEA. A study done in Cambridge, England, compared DHEA and cortisol levels in clinically depressed patients (categorized as “major depressives”) with a matched group of patients in remission from depression and healthy controls. Both morning and evening levels of DHEA were lowest in depressed patients, with inverse correlation between the morning DHEA levels and the severity of the depression. Evening cortisol levels were highest in the depressed group. The low DHEA/cortisol ratio (similar to the shift seen in aging) also characterized the depressed group. The authors point out that DHEA not only antagonizes harmful effects of excess cortisol, but also may have mood improving properties. This may have “significant implications” for the treatment of depression.
Another study on the role of DHEA deficiency in depression focused on recovering alcoholics, a group especially susceptible to depression, and hence to relapse into drinking. The authors found that abstinent alcoholics showed a deficiency of noradrenaline and a low DHEA to cortisol ratio, indicating lower ability to deal with stress. Hypothetically, DHEA might prove a useful adjunct therapy for recovering alcoholics.
There is still some controversy over whether or not DHEA produces cognitive enhancement in humans. Diamond (1999) has suggested that such enhancement may depend on the degree of psychological stress. In his study on rats, DHEA was found to increase hippocampal activity, but only under non-stressful conditions. Stress appears to block the DHEA-induced enhancement.
The ability of DHEA to protect the hippocampus and enhance its activity is important in regard to Alzheimer’s disease. Studies have generally found increased cortisol and lower DHEA in Alzheimer’s disease patients, together with a low DHEA/cortisol ratio. We know that excess cortisol damages the hippocampus and potentiates beta-amyloid toxicity. DHEA is believed to be able to antagonize the destructive effects of excess cortisol. The authors of a recent study have concluded that dementia is correlated with low DHEA more so than with high cortisol. Another study also showed that while the aging process decreases the DHEA/cortisol ratio, victims of dementia have a significantly lower ratio rather the healthy elderly. Based on the opposite effects of cortisol and DHEA on the brain, especially on the
hippocampal region, the authors suggest that it is possible that this pathological imbalance between stress hormones and DHEA accounts for much of the damage.
There has also been some research on the effects of androstenedione, the main metabolite of DHEA, on cognitive enhancement. Androstenedione sulfate has been shown to increase neural activity in certain sections of the rat brain, with implications for memory enhancement and antidepressant action similar to those already found for DHEA.
DHEA’s role in chronic inflammatory diseases
An important overview of the role of DHEA in reducing the damage produced by chronic inflammation was recently published by a team of researchers at the University of Regensburg, Germany. The authors point out that patients with chronic inflammatory diseases such as rheumatoid arthritis show adrenal dysfunction that manifests itself both in insufficient levels of cortisol in response to adrenocorticotropic hormone (ACTH) and low levels of DHEA. With both cortisol and DHEA being too low, the inflammation progresses and leads to harmful consequences.
The current practice is to use synthetic corticosteroids such as prednisolone in an effort to fight chronic inflammation. DHEA remains neglected, in spite of repeated findings of low DHEA levels in patients suffering from chronic inflammatory diseases. But DHEA also plays an important role in preventing inflammation. It is a potent inhibitor of pro-inflammatory cytokines (hormone-like immune chemicals), which in turn signal the immune system and provoke further cellular destruction.
Of special interest is DHEA’s ability to inhibit interleukin 6 (IL-6) and tumor necrosis factor (TNF). These pro-inflammatory cytokines rise with age, and are especially high in patients with inflammatory diseases. IL-6 is known to play a role in promoting bone loss and possibly also joint destruction. In addition, IL-6 promotes the production of certain immune cells which attack the body’s own tissue in autoimmune conditions such as rheumatoid arthritis. High serum IL-6, as seen in rheumatoid arthritis, for instance, is regarded as a reliable biomarker of inflammation. The finding that DHEA supplementation can lower IL-6 makes it a very promising anti-inflammatory agent, especially for chronic disorders which are characterized by significantly elevated IL-6. Besides rheumatoid arthritis, the conditions associated with abnormally high IL-6 include atherosclerosis, osteoporosis, Alzheimer’s disease and certain cancers.
The inverse relationship between DHEA and IL-6 has been confirmed through the study of the menstrual cycle. Serum IL-6 showed a marked rise during the luteal (post-ovulation) phase. This pro-inflammatory cytokine was highest when DHEA levels were lowest, and vice versa.
The primary metabolite of DHEA, androstenedione, has also been found to inhibit the production of IL-6. Likewise, pregnenolone and progesterone also inhibit TNF production.
The deficiency of DHEA in inflammatory diseases also implies a deficiency in peripheral tissue of various sex steroids for which DHEA serves as a precursor. These steroids, both estrogenic and androgenic, are known to have beneficial effects on muscle, bone, blood vessels and so forth. The mainstream therapy with corticosteroids is itself known to lower androgen levels. Consequently, the authors argue that hormone replacement for patients with chronic inflammatory diseases should include not only corticosteroids, but also DHEA.
Other studies also found that adrenal hormones, including DHEA, are of special importance in the treatment of rheumatoid arthritis. There is some evidence pointing to adrenal hypofunction before the onset of rheumatoid arthritis, especially in female patients, who constitute the overwhelming majority of rheumatoid arthritis victims, and whose serum DHEA levels are low (male rheumatoid arthritis patients show low plasma and synovial fluid testosterone). Androgens in general appear to be protective against the development of autoimmune diseases, and DHEA is an important precursor of various androgens. DHEA replacement appears to be especially important for female rheumatoid arthritis patients.
Lupus is another autoimmune inflammatory disease where DHEA (usually in high doses of up to 200 mg) has proven to be a useful adjunct therapy. One author has reviewed the results of all the studies done to date, and concluded that DHEA appears to decrease the requirement for glucocorticoid steroid therapy and somewhat improves symptoms. More important, perhaps, is its protection against bone loss (osteopenia and osteoporosis), as well as improved mental function. Side effects include acne and the lowering of HDL cholesterol (the ratio of HDL to total cholesterol tends to remain the same, however, since LDL cholesterol is also lowered due to DHEA replacement).
Ordinary aches and pains may also be related to low DHEA. When men and women complaining of either lower back pain or neck and shoulder pain were tested, the consistent finding for women was low DHEA and low beta endorphins.
References
Alexandersen P et al. Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circ Res 1999; 84:813-19.
Aragno M et al. Oxidative derangement in rat synaptosomes induced by hyperglycemia: restorative effect of DHEA treatment. Biochem Pharmacol 2000; 60:389-95.
Aragno M et al. DHEA prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats. Diabetes 2000;40:1924-31.
Arlt W et al. DHEA replacement in women with adrenal insufficiency. N Engl J Med 1999; 341:1013-20.
Bednarek-Tupikowska G et al. Influence of DHEA on platelet aggregation, superoxide dismutase activity and serum lipid peroxide concentration in rabbits with induced hypercholesterolemia. Med Sci Monit 2000;6:40-45.
Bittman BB et al. Composite effects of group drumming music therapy on modulation of neuroendocrine-immune parameters in normal subjects. Alternative Ther Health Medicine 2001; 7:38-47.
Boudou P et al. Effects of a single bout of exercise and exercise training on steroid levels in middle-aged type 2 diabetic men: relationship to abdominal adipose tissue distribution and metabolic status. Diebetes Metab 2000; 26:450-57.
Canning MO et al. Opposing effects of DHEA and dexamethasone on the generation of monocyte-derived dendritic cells. Eur J Endocrinol 2000; 143:685-95.
Cardounel A et al. DHEA protects hippocampal neurons against neurotoxin-induced cell death: mechanism of action. Proc Soc Exp Biol Medicine 1999; 222:145-49.
Casson PR et al. DHEA supplementation augments ovarian stimulation in poor responders: a case series. Human Reprod 2000; 15:2129-32.
Christeff N et al. Changes in cortisol/DHEA ratio in HIV-infected men are related to immunological and metabolic perturbations leading to malnutrition and lipodystrophy. Ann N Y Acad Sci 2000; 917:962-70.
Chmielewski V et al. Dexamethasone-induced apoptosis of mouse thymocytes: prevention by native 7alpha-hydrosteroids. Immunol Cell Biol 2000; 78:238-46.
Clemens JW et al. Steroid sulfatase activity in the rat ovary, cultured granulosa and a granulosa cell line. J Steroid Biochem Mol Biol 2000; 75:245-52.
Clerici M et al. Immunoendocrinologic abnormalities in human immunodeficiency virus infection. Ann N Y Acad Sci 2000;917:956-61.
Cutolo M. Sex hormone adjuvant therapy in rheumatoid arthritis. Rheum Dis Clin North Am 2000; 26:881-95.
Diallo K, et al. Inhibition of HIV-1 replication by immunor (IM28), a new analog of DHEA. Nucleosides Nucleotides Nucleic Acids 2000; 19: 2019-24.
Diamond DM et al. The enhancement of hippocampal primed burst potentiation by DHEA-S is blocked by psychological stress. Stress 1999;3:107-21.
Dillon JS et al. DHEA-S and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta cells. Diabetes 2000; 49: 1012-20.
Fabrie, L et al. DHEA and the intracrine formation of androgens and estrogens in peripheral target tissue: its role during aging. Steroids 1998; 63: 322-38.
Feldman HA et al. Low DHEA and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol 2001; 153:79-89.
Ferrari E et al. Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. Eur J Endocrinol 2001; 144:319-29.
Ferrato SJ et al. DHEAS and testosterone: relation to HIV illness stage and progression over one year. J Acquir Immune Defic Syndr 1999; 22: 146-54.
Fiter J et al. Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal women with rheumatoid arthritis. Joint Bone Spine 2000; 67:199-203.
Fraser DA et al. Serum levels of IL-6 and DHEA-S in response to either fasting or a ketogenic diet in rheumatoid arthritis. Clin Exp Rheumatol 2000; 18:357-62.
Garcia-Estrada J et al. DHEA, pregnenolone and sex steroids down-regulate reactive astroglia in the male rat brain after a penetrating brain injury. Int J Dev Neurosci 1999;17: 145-51.
Gianotti L et al. Steroid therapy can modulate gut barrier function, host defenses, and survival in thermally injured mice. J Surg Res 1996; 62:53-8.
Hampl R et al. Immunomodulatory 7-hydroxylated metabolites of DHEA are present in human semen. J Steroid Mol Biol 2000;75:273-76.
Hasseldorf HM et al. Endocrine and immunologic parameters indicative of 6-month prognosis after the onset of low back pain or neck/shoulder pain. Spine 2001; 26:E24-9.
Hayashi T et al. DHEA retards atherosclerosis formation through its conversion to estrogens: the possible role of nitric oxide. Arterioscler Thromb Vasc Biol 2000; 20: 782-92.
Helisten H et al. Accumulation of high-density lipoprotein-derived estradiol-17 fatty esters in low-density lipoprotein particles. J Clin Endocrinol Metab 2001; 86:1294-1300.
Heinz A et al. Severity of depression in abstinent alcoholics is associated with monoamine metabolites and DHEA-S concentrations. Psychiatry Res 1999; 89:97-106.
Hunt PJ. Improvement in mood and fatigue after DHEA replacement in Addison’s disease in a randomized, double-blind trial. J Clin Endocrinol Metab 2000; 85:4650-56.
Jarrar D et al. DHEA: a novel adjunct for the treatment of male trauma patients. Trends Mol Med 2001; 7:81-85.
Kanik KS, Wilder RL. Hormonal alterations in rheumatoid arthritis, including the effects of pregnancy. Rheum Dis Clin North Am 2000; 26: 805-23.
Khalil A et al. Age-related decrease of DHEA concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J Lipid Res 2000; 41:1552-61.
Kipper-Galperin M et al. DHEA selectively inhibits production of tumor necrosis factor alpha and interleukin-6 in astrocytes. Int J Dev Neurosci 1999; 17: 765-75.
Konecna L et al. Modulation of IL-6 production during the menstrual cycle in vivo and in vitro. Brain ehav Immun 2000; 14: 49-61.
Kreze A et al. DHEA, DHEA-S and insulin in acute myocardial infarct. Vnitr Lek 2000; 46:835-8.
Li H et al. DHEA reduces neuronal injury in a rat model of global cerebral ischemia. Brain Res 2001; 888: 263-66.
Michael A et al. Altered salivary DHEA levels in major depression in adults. Biol Psychiatry 2000; 48:989-95.
Monteleone P et al. Plasma levels of neuroactive steroids are icnreased in untread women with anorexia nervosa or bulimia nervosa. Psychosom Medicine 2001; 63:62-8.
Murialdo G et al. Hippocampal perfusion and pituitary-adrenal axis in Alzheimer’s disease. Neuropsychobiology 2000; 42:51-57.
Nagata C et al. Serum concentrations of estradiol and DHEA-S and soy product intake in relation to psychologic well-being in peri- and postmenopausal Japanese women. Metabolism 2000; 49:1561-64.
Overbeck R et al. DHEA decreases mortality rate and improves cellular immune function during polymicrobial sepsis. Crit Care Medicine 2001; 29:380-84.
Padgett DA et al. Steroid hormone regulation of antiviral immunity. Ann N Y Acad Sci 2000; 917:935-43.
Porsova-Dutoit I et al. Do DHEA/DHEA-S play a protective role in coronary heart disease? Physiol Res 2000; 49 Suppl 1:S43-56.
Schatzl G. Endocrine patterns in patients with benign and malignant prostatic diseases. Prostate 2000; 44:219-24.
Schifitto G et al. Autonomic performance and DHEAS levels in HIV-1-infected individuals: relationship to TH1 and TH2 cytokine profile. Arch Neurol 2000; 57: 1027-32.
Shin S et al. DHEA and melatonin prevent Bacilllus anthracis lethal toxin-induced TNF production in macrophages. Cell Biol Toxicol 2000; 16: 165-74.
Smith KJ, Skelton HG. Peroxisomal proliferator-activated ligand therapy for HIV lipodystrophy. Clin Exp Dermatol 2001; 26:155-61.
Straub RH et al. Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases – substitutes of adrenal and sex hormones. Z Rheumatol 2000; 59 Supplement 2:108-18.
Straub RH et al. Serum DHEA and DHEA-S are negatively correlated with serum IL-6, and DHEA inhibits secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 1998; 83:2012-17.
Swenson CD et al. Relationship between humoral immunoaugmenting properties of DHEAS and IgD-receptor expression in young and aged mice. Ann NY Acad Sci 1995; 774:249-58.
Urbanoski K et al. Androstenedione sulfate increases dentate gyrus population spike amplitude following tetanic stimulation. Physiol Behav 2000; 71:435-440.
Van Vollenhoven RF. DHEA in systemic lupus erythematosus. Rheum dis Clin North Am 2000;26:349-62.
Verthelyi D, Klinman DM. Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo. Immunology 2000; 100:384-90.
Whitnall MH et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int J Immunopharmacol 2000; 22:1-14.
Yang JV et al. Inhibition of HIV-1 latency reactivation by DHEA and an analog of DHEA. AIDS Res Hum Retroviruses 1993; 9:747-54.
Wang M et al. Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT. Int J Oncol 1999;14:1185-95.
Zhang Z et al. Prevention of immune dysfunction and Vitamin E loss by DHEA and melatonin supplementation during murine retrovirus infection. Immunology 1999; 96:2911-17.

 
 
 
 
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DHEA may protect men’s hearts from disease, says new study

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Houston: The steroid hormone, dehydroepiandrosterone, commonly known as DHEA, does protect against the risk of cardiovascular events in men, according to a new Swedish study.
The Endocrine Society’s 94th Annual Meeting held in Houston heard about the  protective effect of higher levels DHEA.
The hormone which is produced by the adrenal glands, acts a precursor to the hormones estradiol and testosterone. Previouslysome research findings have suggested an association between increased DHEA levels and a reduction in heart disease, but the majority of the studies involving DHEA have been small and results have not always been conclusive.
In Sweden Ă…sa Tivesten, MD, PhD of the University of Gothenburg i and colleagues analysed data from 2,416 men between the ages of 69 and 81 years enrolled in the Osteoporotic Fractures in Men Sweden study, designed to evaluate risk factors for several diseases. Blood samples obtained upon enrollment were analyzed for DHEA and DHEA sulfate (DHEA-S)–the sulfate ester of DHEA which is the form of the hormone that occurs predominantly in the blood.
Over a five year follow-up period, 485 cases of fatal or nonfatal cardiovascular events were documented. Having a higher serum DHEA was associated with a lower risk of cardiovascular events, as was having a higher level of DHEA-S. Men whose DHEA-S was among the lowest one-fourth participants had a 25 percent higher risk of events compared to the rest of the subjects, and those whose levels of both DHEA and DHEA-S were among the lowest fourth had a 34 percent higher risk of any major cardiovascular event, and a 41 percent higher risk of a cerebrovascular event compared to the remainder of the group.
Dr Tivesten, an associate professor said: “Our findings may be the result of DHEA-S being protective, or that lower DHEA-S level is a marker for poor general health.’
She added that more research is needed to understand underlying mechanisms and to evaluate the potential benefits of hormone replacement.
“We cannot say that DHEA-S is protective because we have only studied an association,” she added. “A potential practical implication is that established cardiovascular risk factors perhaps should be assessed and treated more aggressively in men with lower DHEA-S levels. However, this must be evaluated in future studies; today, DHEA-S level is not part of cardiovascular-risk assessment.”
Want to know more about the health benefits of DHEA click here
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DHEA – anti-ageing experts criticise flawed report

Fort Lauderdale: The war between those who advocate natural approaches to disease prevention as opposed to proponents of synthetic drugs continues unabated. At stake are the lives of millions of aging humans who are confronted with institutional propaganda aimed at discrediting therapies that are not FDA approved.

As health-conscious Americans are well aware, a large volume of published research documents significant benefits when aging humans restore DHEA and testosterone hormones to youthful levels.

On October 19, 2006, however, the media reported on a very small study that showed only miniscule results in aging humans who received either DHEA or low-dose testosterone. In response to this one study, the media declared that these hormones are “no fountain of youth”.1

This one study showing only small benefits to DHEA or testosterone supplementation had serious design flaws that invalidate its conclusions. The newscasters failed to consider these flaws when proclaiming there is “no reason for older people to continue taking DHEA.”

In todayÂ’s media frenzied world, scientific journalism is practiced by ambush. The very day a medical study is published, it can become the headline news story of the day. This denies an opportunity for those who might disagree with the studyÂ’s design and methodologies to rebut what might be junk science. In the case of this recent study questioning the use of DHEA and testosterone, the flaws are so significant as to cause its findings to have little or no meaning.

This article represents Life ExtensionÂ’s initial rebuttal to the recent attack on DHEA and testosterone.

Flaw Number One: Factors Affecting Bone Mass Ignored

One of the anti-aging parameters tested in this study was the effects of DHEA or testosterone on bone mineral density.

Compared to placebo, the study found that in women supplemented with DHEA, there was a small, but significant increase in bone mineral density of the ultradistal radius (a wrist bone). Men who supplemented with DHEA had a small, but significant increase in the bone mineral density of the femoral neck. (The “femoral neck” connects the shaft of the femur bone to the ball part of the femur in the hip.)

Men who supplemented with testosterone had a significant increase in the bone mineral density of the femoral neck. No increase in bone mineral density was found in the spine or total femur in those who supplemented with DHEA or testosterone.

Based on these findings, the media declared DHEA and testosterone worthless, despite the fact that there was improvement in several measurements of bone mineral density. When viewed in the context of data from previous studies showing significant bone benefit in response to DHEA-testosterone, the findings from this recent study help confirm the effects that these two hormones confer on bone health.

The biggest problem with this study parameter, however, is that it only looked at DHEA or testosterone compared to placebo. It did not monitor the study subjects to ascertain what else they might be doing that would affect their bone density.

As any health-conscious consumer knows, there are many more factors involved in maintaining bone density than just DHEA and testosterone. The study failed to assess diet or the intake of nutrients involved in bone density such as calcium, vitamin D, magnesium, and vitamin K when comparing those who took DHEA or testosterone to the placebo group.

Due to the small size of this study (87 men and 57 women), there is a very real chance that there were differences in terms of bone-protecting nutrient intake between the two groups. This means that it is possible that subjects in the placebo arm may have taken more calcium, vitamin D, vitamin K, magnesium, etc. than those in the DHEA and/or testosterone group. The failure to specifically control for bone-building nutrient intake points to one of several flaws in the study design.

Flaw Number Two: Factors Affecting Body Composition Ignored

Another anti-aging parameter this study looked at was the effects of DHEA or testosterone on body fat and muscle mass.

Compared to placebo, elderly men supplemented with DHEA had a decrease in the proportion of body fat (as measured by fat-free mass). When the male and female groups were combined, the DHEA group had a small but significant decrease in the proportion of body fat. Men in the testosterone group had a significant reduction in body fat (as measured by fat-free mass).

These findings confirm previous studies showing reductions in body fat in those supplementing with DHEA or testosterone. For example, a recent 2004 study showed that DHEA supplementation in aging men and women was associated with significant reductions in abdominal fat as well as improvements in insulin sensitivity.2

When measuring another area of body composition, women receiving DHEA showed a 9.2 cm2 increase of lean thigh muscle area compared to a 3.5 cm2 decrease in the placebo group. However, because women in the placebo group already had higher thigh-muscle area than in the DHEA group at baseline, the study authors concluded that DHEA had no effect on thigh-muscle area. This conclusion is particularly biased when one considers that lean muscle mass in the thigh of women treated with DHEA was higher than the placebo group at the end of the study, even though the DHEA group had a less lean muscle mass at the beginning of the study compared to placebo.

Despite these favorable body composition findings, the media stated that consumers who bought DHEA supplements were receiving no value. Not only is this another false conclusion, but the failure of the study design to assess calorie intake, types of calories consumed, and other factors involved in body fat composition renders even these modest reductions in body fat highly suspect. In other words, since this was such a small study, if just a few participants in either the DHEA or testosterone group increased calorie intake, or altered their diet to cause increases in body fat, this could have skewed the results significantly. If on the other hand, just a few participants in the placebo group reduced their calorie intake, this would have distorted the final results even more.

Further twisting the findings related to body composition was the criteria that excluded anyone from participating in the study who engaged in exercise lasting more than 20 minutes more than two times a week. Exercise is an important component of an anti-aging program, and excluding those who regularly engage in exercise helped ensure that neither the active or placebo group would demonstrate significant changes.

We know that DHEA works to enhance the benefits of exercise. For example, a recent study showed that DHEA potentiated the effect of 4 months of weight-lifting training on muscle strength and on thigh muscle mass.3

The failure of the study design to incorporate both DHEA and exercise to build bone and muscle mass is embarrassing from a scientific standpoint, and highlights another defect in the trial design.

Flaw Number Three: No Individualized Program

In this recent study, all participants received the exact same dose of DHEA or testosterone for two straight years. It did not matter if individual blood levels skyrocketed too high or failed to even reach minimum levels needed to achieve efficacy. As far as the designers of this study were concerned, one size (i.e., the same dose) fits all.

Hormone requirements vary considerably between individuals. Some people, for instance, only need 15 mg/day of DHEA, while others require over 100 mg/day to attain similar blood levels. In this study, all male participants in the active group were given 75 mg/day of DHEA or 5 mg/day of transdermal testosterone. All women participants in the active group were given 50 mg/day of DHEA.

Based on reviewing thousands of blood test results of people taking DHEA and/or testosterone, Life Extension researchers have observed huge variations in individual responses to DHEA and testosterone supplemental intake. This has also been confirmed by the hundreds of practicing physicians who prescribe these hormones and then do follow-up blood tests to make sure their patients achieve optimal hormone balance.

There was no attempt to achieve optimal blood levels of DHEA or testosterone in these study participants. The sole objective of this study was to give each participant in the active group the exact same dose of hormone(s) and then monitor some of the effects compared to placebo. We at Life Extension view the failure to use blood test results to adjust individual hormone dosing as the equivalent of target shooting while blindfolded and then saying it is impossible to consistently hit the target.

The fact that the conventional doctors who designed this study failed to factor in the need for individualized dosing is not surprising. For decades, physicians have prescribed the same dose of estrogen and other drugs to patients regardless of individual need. Despite the existence of millions of copies of books that specify how DHEA-testosterone should be properly dosed, the doctors who designed this flawed study failed to adjust the amount of DHEA-testosterone given to study subjects based on individual blood readings. Nor was there even a mention of the fact that doctors who prescribe these hormones do indeed adjust doses based on blood or saliva test results.

The flawed methodology applied to dosing DHEA and testosterone from this trial is another defect in trial design. Yet, this egregious error did not stop the headline hungry media from vilifying DHEA and testosterone.
Flaw Number Four: Failure to Suppress Excess Estrogen
As men mature past age 50, an enzyme called aromatase increases in their bodies.

The aromatase enzyme converts testosterone to estrogen. When testosterone drugs are given to aging men, the aromatase enzyme can convert the testosterone into excess estrogen, which causes undesirable effects.
One problem with excess estrogen in aging men is that the balance of testosterone to estrogen is disrupted, with the excess estrogen contributing to feminizing effects in aging men.

In the study the media used to attack DHEA-testosterone, levels of estrogen increased dramatically in both men and women in the active group as opposed to the placebo group. Instead of carefully assessing individual response and taking steps such as reducing the dose of DHEA or prescribing aromatase-inhibitors (such the drug Arimidex® or nutrients like zinc, nettle, and chrysin) in response to high estrogen levels, many study participants were allowed to continue with undesirably high estrogen levels.

Interestingly, some beneficial effects were shown in the active (DHEA or testosterone) groups, despite the high levels of estrogen that manifested. Had aromatase inhibitors been used in the male group where appropriate, and DHEA dosing reduced in the female group when estrogen levels increased too much, the beneficial effects of DHEA or testosterone could have been exponentially enhanced.
The failure to protect against excess estrogen production in response to DHEA or testosterone therapy invalidates this studyÂ’s findings. The media, however, never gave the experts on anti-aging medicine an opportunity to point out this significant flaw.

The mediaÂ’s biased assassination of DHEA-testosterone will result in most aging Americans remembering their newscaster proclaiming that hormone restoration is a waste of money. There was no scientific debateÂ…just a public relations coup by todayÂ’s prescription drug-financed medical establishment.

Flaw Number Five: Testosterone Not Restored to Youthful Levels

In studies showing dramatic anti-aging effects in response to testosterone therapy, levels of testosterone were restored to youthful ranges (500-1200 ng/dL). Subjects receiving testosterone in this recent flawed study only increased their total blood testosterone levels from 357 ng/dL to 461 ng/dLÂ… well below optimal youthful ranges.

Median levels of biologically active free testosterone remained below normal youthful ranges throughout the study and did not reach the higher levels recommended by anti-aging experts.

The authors of the study acknowledged that they gave these men low doses of testosterone when stating in their conclusion: “Additional long-term studies of testosterone are warranted to determine the risk-benefit ratio of higher doses.”

Despite the obvious failure to adequately increase testosterone blood levels, the media participated in this hoax to deceive American men into believing that they should not replenish the testosterone lost to aging. This is great news for pharmaceutical companies who stand to sell a lot more prescription drugs that treat associated problems related to suboptimal hormone levels such as sexual health, depression, cardiovascular health, neurological disorders, and the many chronic inflammatory conditions that can all be effectively prevented by correcting the underlying hormonal deficiency in the first place.

Flaw Number Six: Inadequate Numbers of Study Subjects to Assess Quality of Life.

Another anti-aging parameter of this study looked at quality of life scores and found no improvement.
Previous studies, however, tested these hormones on people suffering from depression and other quality of life problems. These previous studies showed that DHEA or testosterone was effective in people who suffered from these disorders. For example, a 2005 study showed that in middle-aged men and women suffering from minor and major depression, DHEA significantly reduced depression scores and improved sexual function scores as against the placebo group.4

The fact that individuals not suffering from these disorders did not report improvements in their quality of life scores could have been due to faulty data collection or the very small study size.

In fact, the editorial that accompanied this study stated that there were too few subjects enrolled to detect clinically meaningful differences in this quality of life parameter. This same editorial, however, also called for DHEA to be regulated as a prescription drug.

Flaw Number Seven: Inadequate numbers of study subjects to assess effects on glucose control

Type II diabetes is characterized by systemic insulin resistance that results in chronic hyperglycemia (excess blood sugar). Previous studies indicate that DHEA and testosterone protect against insulin resistance. For example, a 2003 trial showed that 25 mg of DHEA improved insulin sensitivity as well as endothelial function in hypercholesterolemic men.5

In this study on healthy people, DHEA or testosterone did not improve markers related to insulin resistance. The fact that the study size was very small may explain why the finding of this study parameter was neutral.

Flaw Number Eight: Increases in Physical Strength Downplayed
Compared to baselines, men and women taking DHEA could chest press 4.99 pounds more weight than the placebo group after two years. Men receiving low-dose testosterone were able to chest press 9.99 more pounds compared to the placebo group after two years.

The studyÂ’s authors downplayed these improvements by stating three months of resistance exercise training increased chest press strength by an average of 33 pounds in older people.

The contradiction is that the study subjects were not allowed to participate in more than 20 minutes of exercise more than two times a week. This restriction would have severely limited an improvement in physical strength, yet even with this exercise restriction, there was still a measurable improvement in physical strength in those receiving DHEA or testosterone compared to placeboÂ…a fact the media choose to ignore when attacking the use of these hormones for anti-aging purposes.

Flaw Number Nine: It Takes More Than Hormones to Slow Aging Parameters

There are 14 independent causes of aging that have been identified. The good news is that there are ways of at least partially protecting against each one of these 14 different causes of age-related degeneration.

As has been the case with previous flawed studies, conventional doctors restrict test subjects to a single approach that might beneficially affect some aging parameters. When that single approach fails to produce significant results, the medical establishment (and the media) proclaims the nutrient or hormone to be worthless.

Patients that visit anti-aging doctors for hormone replacement therapy are prescribed a lot more than just DHEA or testosterone. They are often put on comprehensive programs that involve dietary changes, exercise, synergistic hormone modulating drugs-nutrients, replacement of other hormones lost to aging (like progesterone, pregnenolone, thyroid), and dietary supplements (like CoQ10, carnitine, lipoic acid, carnosine, fish oil) that address specific age-accelerating mechanisms.

The design of this study virtually guaranteed failure since it only provided subjects with DHEA or low-dose testosterone. An absolute consensus amongst those in the anti-aging community is that a lot more than sub-optimal hormone therapy is required to slow and partially reverse aging, though proper hormone balancing is a critical component of an overall program.

The appendix at the end of this article articulates the 14 independent causes of aging and what can be done to partially counteract them. When reviewing these pathological mechanisms involved in normal aging, it would be absurd to assume that miraculous results could be obtained by correcting only one of them (i.e. hormone imbalance), as was done in this flawed study.

Flaw Number Ten: Study Did Not Evaluate All of DHEAÂ’s Effects

Conventional doctors and the media took the mediocre findings from this flawed study and concluded that DHEA or testosterone replacement is of no value to elderly humans. Yet the parameters used in the study to assess aging were limited to:
1. Bone mineral density
2. Body fat-muscle composition
3. Quality of life scores
4. Insulin resistance and glucose tolerance
5. Physical performance

Despite the failure to customize the dose of DHEA or testosterone based on individual need, the failure to protect against excess estrogen, the failure to assess for other independent factors (such as the effect of food intake on body fat mass), the failure to achieve optimized blood levels of these hormones, and the failure to account for nutrients needed to maintain or restore these narrow parameters of aging (such as whether test subjects were taking calcium/vitamin D to build bone), there was still some benefit shown in the DHEA and testosterone groups.

What was blatantly omitted from the attack on DHEA-testosterone was the fact that aging individuals take these hormones for purposes that go beyond the narrow parameters evaluated in this study. For instance, DHEA has long been used to help maintain neurological, sexual, and immune function in those going through normal aging processes and those afflicted with certain disorders. The most striking benefit associated with DHEA (and testosterone), however, may have to do with protecting against endothelial dysfunction that can lead to heart attack, stroke, and other vascular diseases.

How many lives might be lost?

The two-year study used to vilify DHEA only had 87 male participants, with one-third of the subjects receiving placebo. Based on this one study, conventional doctors are calling for DHEA to be removed from the marketplace and turned into a prescription drug. There were no adverse effects reported during this study.

Overlooked by the media are the hundreds of studies showing significant benefits to those who maintain higher DHEA or testosterone blood levels. For example, in a larger study involving 1,700 aging males carried out over nine-years, those with the lowest levels of DHEA were 60% more likely to develop coronary artery disease.6

About one million people die from a vascular-related disease each year

Compelling evidence indicates that many of these deaths could be prevented if aging men maintained their DHEA and testosterone in more youthful ranges. If DHEA-testosterone reduced these deaths by only 20%, then about 200,000 American lives could be saved each year.

DonÂ’t Be a Victim of Drug Company Propaganda

In response to this flawed study, conventional doctors are calling for the FDA to regulate DHEA as a prescription drug. Despite this study showing no adverse effects from DHEA or testosterone, the rationale is that people are being “ripped off” when they are sold these hormones for anti-aging purposes. This drastic conclusion flies in the face of hundreds of published studies validating the anti-aging benefits in response to DHEA and testosterone restoration.

There is little subtlety in what these mainstream doctors are really trying to accomplish. They make it clear that based on this one study, prescription “bisphosphonate” drugs would re-build bone better than natural hormone replacement. While bisphosphonate drugs have a role in preventing cancer metastasis to the bone, they are very expensive and cause serious side effects in some people. DHEA, on the other hand, is so cheap it is difficult to credibly claim that anyone is being “ripped off” when buying it, as one doctor was quoted as stating.

It is in the economic interest of the pharmaceutical industry to see restrictions placed on DHEA and testosterone as there would be a surge of age-related diseases if free access to these hormones were to be denied. This increase in age-related disease would directly correlate with the widespread deficiencies of DHEA and testosterone that would occur if consumer access to these hormones was impeded by governmental edict.

Financial Conflicts of Interest

Some of the authors of the flawed study on DHEA and testosterone have connections to the pharmaceutical industry, and drug money lobbyists can heavily influence how these studies are designed.

The doctor who most viciously attacked DHEA, stating that consumers were being “ripped-off” when buying it, admitted to receiving consulting fees and/or grants from drug companies that include Pfizer, Novo Nordisk, Novartis, and Duocort.7

While all these companies sell drugs whose sales would be adversely affected if more people used DHEA, the Duocort pharmaceutical company’s website specifically states that it is developing drugs aimed at “chronic adrenal hormone replacement therapy.” DHEA is synthesized primarily in the adrenal glands. DHEA is used by aging people because after age 30, there is a chronic deficiency in adrenal DHEA production.

While DuocortÂ’s public focus is on developing long-acting glucocorticoid drugs to treat adrenal insufficiency, it seems more than a coincidence that the most vocal critic of DHEA supplements has received consulting fees from a company whose website states:

“Treatment of adrenal insufficiency involves replacing, or substituting, the hormones that the adrenal glands are not making.”
Based on conventional medicineÂ’s logic, it is alright to replace hormones (like DHEA) the adrenal glands are not making as long as the replacement is a patented prescription drug. The news media totally overlooked these financial conflicts of interest when regurgitating the anti-DHEA propaganda of doctors on the payroll of the pharmaceutical industry.

Conclusion

In response to a plethora of positive studies linking higher DHEA levels to lower degenerative disease risk,8-33 DHEA has become an enormously popular low cost dietary supplement. The use of testosterone enhancing products by aging men has aalso grown exponentially over the past decade.

An evaluation of the recent study that questions the anti-aging efficacy of DHEA and testosterone reveals serious flaws that invalidate the studyÂ’s findings. Despite these flaws, the actual findings show a small but significant benefit to DHEA-testosterone when measuring certain parameters related to aging.

The media choose to downplay the benefits demonstrated in this study and instead launched an attack against the use of DHEA-testosterone for anti-aging purposes.
Proponents of natural hormone restoration have been very clear about the need to achieve optimal levels of testosterone and DHEA. The subjects in this recent study were not individually dosed and therefore did not come anywhere close to achieving optimal blood levels. It is thus no surprise that the results of this flawed study are inconsistent with the known health benefits of DHEA.

The financial existence of drug companies is dependent on substantial numbers of aging Americans contracting degenerative diseases. Drug companies therefore have an economic interest in finding ways to discourage and even criminalize the use of youth hormones that protect against age-related disease. For instance, if DHEA and testosterone supplementation only lowered cardiovascular disease rates by 20%, the drug industry would face billions of dollars in lost profits, as sales of drugs used to treat vascular diseases would be correspondingly reduced.

In an attempt to discredit the benefits of natural hormone restoration, conventional doctors, some with direct financial links to the pharmaceutical industry, sought to mischaracterize the findings from this very small and flawed study on elderly men and women.

The downplaying of the beneficial findings found in this study, along with ten specific flaws that invalidate its results, represents a biased attempt to discourage aging Americans from maintaining or restoring youthful hormone balance.

DHEA does not help lean body mass in ageing

New york: The popular anti-aging supplement DHEA is of little value in preventing age-related bone and muscle changes, according to new research.

In the study published in the New England Journal of Medicine (NEJM), taking supplements of dehydroepiandrosterone (DHEA) has no demonstrable benefit on muscle strength, peak endurance, bone mass, muscle mass, glucose tolerance or quality of life. The study was conducted by Mayo Clinic.

To arrive at its data and conclusions, the study evaluated a group of 87 men older than 60 and 57 women older than 60 over a two-year period. The people chosen in the study all had low DHEA levels prior to the study.

Taking DHEA did raise the study participants’ DHEA to high normal levels. However, those higher levels did not result in significant body-composition measurements, peak volume of oxygen consumed per minute, muscle strength or glucose tolerance. The study reported no improvement for quality of life. No major adverse effects were observed from taking DHEA.

Men in the study also were given low doses of testosterone; that appeared to result in a small increase in bone density.

Your body converts DHEA into the sex hormones estrogen and testosterone. Proponents of DHEA say it also slows aging, increases muscle and bone strength, burns fats, improves cognition, bolsters immunity and protects against chronic diseases.

In an editorial accompanying the study results, NEJM recommended that because DHEA does show some benefit in people who have problems with their adrenal glands, it should be regulated as a drug and no longer considered a food supplement.

Prior research hasn’t supported taking DHEA for anti-aging benefits. In fact, prior research has shown that DHEA carries risks and may cause side effects. This latest research confirms that taking DHEA does not provide benefits for body composition, physical performance or quality of life.

Melatonin No 1 anti-ageing ‘drug’

Fort Lauderdale: Melatonin has been named the top anti-ageing drug in a list of 10 recommended by the US’s Life Extension Foundation, leading experts on anti-ageing therapies.

The availability of these hormones and supplements varies from country to country and some are only available through prescription from a qualified physician.

Anyone embarking on a life extension programme using hormones and supplements is advised to seek a blood test from an anti-ageing physician to check their biomarkers so that the correct levels of supplementation are taken.

LIFE EXTENSION DRUG NUMBER 10
SYNTHETIC HUMAN GROWTH HORMONE

Injections of synthetic human growth hormone have been used by geriatric physicians to rejuvenate aging men by increasing their muscle mass, strength, flexibility, and coordination.

Growth hormone deficiency is a major cause of the decline in immune function and protein synthesis with advancing age in both muscle and neurologic tissues. Recent findings suggest that growth hormone may be an effective treatment for early-stage Alzheimer’s disease as well as early senile dementia caused by a decline in brain cell energy metabolism. We will soon be reporting on clinical benefits reported with growth hormone therapy in both Alzheimer’s and Parkinson’s patients.

If growth hormone were not artificially overpriced because of the FDA restriction of its sale in the United States, we might have placed it higher on our list. It doesn’t cost any more to synthesize growth hormone than it does to synthesize insulin. Without FDA interference, most aging Americans could easily afford injections of growth hormone in an attempt to slow aging. The need to inject growth hormone also limits the availability of this highly potent life extension drug.

The current cost of synthetic human growth hormone ranges from $12,000-225,000 annually.

LIFE EXTENSION DRUG NUMBER 9
PIRACETAM

The most frequently used offshore drug to boost short-term memory and overall cognitive function is piracetam.

There are more than 800 published studies documenting the ability of piracetam to promote youthful neurologic function, including enhanced cellular protein synthesis and interhemispheric and intercellular communication.

Stroke victims might avoid paralysis and death if given drugs like piracetam after entering the hospital. Even in patients who suffered stroke-induced brain cell injury years ago, there is evidence that piracetam may help to improve the functioning of these damaged cells. Piracetam can be ordered in Europe.

LIFE EXTENSION DRUG NUMBER 8
DHEA
Because of some recently published studies in elderly humans, the news media have been touting the multi-faceted anti-aging benefits of DHEA (dehydroepiandrosterone).

DHEA is now fulfilling much of the promise indicated in the animal studies that Saul Kent and The Life Extension Foundation have been informing our members about since 1975.

For those suffering from adult-onset diabetes, atherosclerosis, Parkinson’s and Alzheimer’s disease, or any form of autoimmune disease such as multiple sclerosis or lupus, DHEA replacement therapy is highly recommended.

DHEA can be expensive for people who need high doses, but for most people it is reasonably priced. We recommend blood tests to measure the effect that DHEA supplementation has on your DHEA serum level. While these tests currently cost $55-$110, they can save you money by enabling you to lower your daily dose of DHEA. Men should also have more regular PSA (prostate specific antigen) tests to make sure they do not have prostate cancer.

It is regrettable that we have had to advise men with prostate cancer to avoid DHEA because it could increase testosterone (and subsequently dihydrotestosterone levels), which could accelerate the proliferation of prostate cancer cells. For all men taking DHEA, we suggest supplementation with SERENX (saw palmetto extract) to block the conversion of testosterone into the more dangerous dihydrotestosterone.

SERENX (also called PERMIXON) has not been listed in the top ten because it is not an appropriate therapy for most women. However, for men over 40, we strongly recommend the daily intake of 1 -2 capsules of low cost SERENX to prevent benign prostatic hypertrophy and possibly prostate cancer.

If DHEA was completely free of side effects, and did not require blood testing, LEF says it would be listed higher. It is a well substantiated life extension therapy that can help to protect us against many of the degenerative diseases associated with aging, and may have an effect on aging itself.

LIFE EXTENSION DRUG NUMBER 7
VINPOCETINE-HYDERGINE
These two drugs provide a wide range of anti-aging effects in brain and other cells that you cannot easily obtain with any other therapy.
Vinpocetine and/or Hydergine have been shown to:
* improve blood supply to the brain
* increase the amount of oxygen delivered to the brain
* increase oxygen use by the brain
* enhance metabolism in brain cells
* protect the brain from damage during periods of decreased and/or insufficient oxygen supply
* slow the deposit of age pigment (lipofuscin) in the brain
* prevent free radical damage in brain cells
* increase intelligence, memory, learning, and recall
* enhance the use of glucose by brain cells
* increase ATP levels in the brain
* stop blood from becoming sticky
* raise brain levels of serotonin

Vinpocetine is rather expensive (at 20-40 mg a day), which is one reason we don’t list it any higher. Vinpocetine has been on the world market since the early 1980s, but as far as we know, has yet to be entered in the FDA’s new drug approval quagmire. The cost of this periwinkle herbal extract would be very little if the FDA didn’t interfere with the shipment of drugs from overseas companies. We are currently seeking a standardized periwinkle extract that we could sell as a low cost nutrient just as we do with acetyl-l-carnitine and melatonin.

Hydergine is more affordable at effective dose ranges of 4 to 12 mg a day. Most generic brands of ergoloid mesylate are comparable to the Sandoz “Hydergine” brand.

LIFE EXTENSION DRUG NUMBER 6
LIFE EXTENSION DRUG GH3 or K.H.3

GH3 and K.H.3 are popular products whose active agent is procaine, an anti-aging compound discovered in the 1950s by Romanian physician Ana Asian. Both GH3 and K.H.3 suppress monoamine oxidase (MAO) levels. Elevated MAO destroys the essential neurotransmitters dopamine and norepinephrine. GH3 or KH3 also suppress elevated serum cortisol levels, which has been linked to several of the degenerative diseases of aging. There are better cortisol suppressing therapies such as low dose RU486, but at this time, RU-486 is not available to Americans.

GH3 and K.H.3 can be taken every day including the days you take deprenyl, which is a selective MAO inhibitor. An appropriate dose of these drugs is one to two GH3 or KH3 tablets daily. Some doctors believe you should take a five day break from these drugs once a month to avoid too much monoamine oxidase suppression, but our review of the scientific literature does not support the need for taking such a break.

LIFE EXTENSION DRUG NUMBER 5
CENTROPHENOXINE

Lifespan studies have documented specific anti-aging properties for the combination of DMAE and p-chlorophenoxyacetate, the two active ingredients that make up centrophenoxine, a potent life extension drug sold under several names, including Lucidril.

Centrophenoxine has extended the lifespan of laboratory mice and has been shown to reduce a type of cellular debris called lipofuscin (aging pigment) in the neurons that populate our brain and central nervous system. The excessive accumulation of lipofuscin with advancing age has been linked to age-related neurologic diseases.

Centrophenoxine speeds up information processing in the brain and enhances brain cell uptake of glucose. Brain cells use glucose to produce the energy they need to perform their neurological functions and to maintain cell viability.

Some People cannot tolerate even one tablet a day of centrophenoxine, while others can take 1-4 tablets a day and experience dramatic cognitive and energy enhancing effects.

Centrophenoxine can be ordered from European sources at affordable prices.

LIFE EXTENSION DRUG NUMBER 4
PHOSPHATIDYLSERINE

Phosphatidylserine (PS) is sold as a drug in Europe at outrageously high prices. The standardized PS extract now available as a dietary supplement is less expensive than the European “drug”, but is still a pricey item.

We have written extensively about the anti-aging benefits of PS later in this September edition of Life Extension Update and want to reiterate that PS may produce a cumulative effect that could enable people to reduce their dosage of the drug after attaining the desired cognitive enhancing benefits.

Standardized PS extract is contained in the new COGNITEX and is available in bottles of 100 mg soft-gel caps.

LIFE EXTENSION DRUG NUMBER 3
DEPRENYL(Also known as Eldepryl)

This was a hard one to call. A good argument could be made for deprenyl being Life Extension Drug Number 2, but we based this decision strictly on the published evidence we have today. A new study tomorrow could cause us to move deprenyl to number 2.

Deprenyl has produced dramatic life extension effects in animals, but we are fairly certain that deprenyl alone will not do as well in humans. The reason for this is that in rats, the elevation of monoamine oxidase (MAO) plays a greater role in the aging process than in humans. Deprenyl is a potent, selective inhibitor of MAO-B, the type of MAO that damages brain cells during “normal” aging.

Life Extensionists take deprenyl to help prevent Parkinson’s disease and the symptoms of aging that are very similar to those suffered by Parkinson’s patients. There is solid evidence that deprenyl protects many types of brain cells from premature aging and death. There is also evidence that deprenyl boosts cellular production of SOD and catalase, the natural antioxidant enzymes that are depleted in aging.

Our current protocol calls for 2-5 deprenyl tablets (5 mg) a week for those in their 40s. The older you are, the more deprenyl you should take, but it is advisable not to take more than one 5-mg tablet (or capsule) of deprenyl a day unless you have the early symptoms of Parkinson’s or Alzheimer’s disease. In this case, you should take 10 mg of deprenyl a day under the supervision of a physician.

LIFE EXTENSION DRUG NUMBER 2
ACETYL-L-CARNITINE
There are too many new studies appearing in the scientific literature about acetyl-l-carnitine for life extensionists not to take this enhanced amino acid compound that enters the blood stream and penetrates cell membranes more effectively than regular I-carnitine.

Acetyl-l-carnitine is beneficial to heart muscle cells, immune function and probably enhances energy production in every cell of the body. The multi-faceted benefits of acetyl-l-carnitine in brain cells makes it the single most important supplement we can take to maintain and improve overall neurological function.

Acetyl-l-carnitine has been shown to improve neurological function even after we stop taking it, suggesting that acetyl-l-carnitine may re-program neuronal and neurotransmitter functions to enable the brain to function in a more youthful, energetic state.

We suggest that healthy members go on at least two 50-day cycles (2 capsules each day) of acetyl-l-carnitine supplementation every year. If you can afford to take acetyl-l-carnitine more often, this should produce greater benefits.

LIFE EXTENSION DRUG NUMBER 1
MELATONIN

Melatonin is the most documented anti-aging therapy in the world.

It not only protects us against neurological aging, but possibly protects us against every age-related disease known to mankind. It is a highly potent antioxidant, has been shown to protect against various forms of cancer, and has extended lifespan in laboratory animals. Melatonin has also been used by physicians at high doses as an effective treatment for a wide variety of diseases. We will soon be carrying an exclusive story about one of these physicians who has been using melatonin for over 15 years in his research. There has been no evidence of toxicity in any of the published studies of melatonin that we have seen.

Melatonin costs very little. The Life Extension Buyers Club uses only ultra pure pharmaceutical-grade melatonin that costs us 40% more than lower grade melatonin. This ultra pure melatonin goes through additional purification processes that makes it almost 100% pure (99.8% to 99.9% certified purity), yet the cost for this premium melatonin is still less than $5.00 a month for most people.

There are still dedicated life extensionists who do not take melatonin because they think it is only useful for the treatment of insomnia. Melatonin is effective in about 80% of people suffering from insomnia, and is highly effective in preventing the symptoms of jet lag. However, we strongly suggest that people who do not suffer from insomnia take at least a 1 mg of melatonin every night. The cost of melatonin is too low for anyone seriously following a life extension program not to use it. A two-month supply of 1 mg melatonin capsules costs just $4.50

There are some people who should not take melatonin. Here are the conditions where melatonin might be contraindicated :
* children (unless recommended by a doctor)
* pregnant women
* people under the age of 30
* people with seasonal affective disorders (SAD)
* people with acute schizophrenia
* manic patients
* possibly those with ovarian or immune system cancers such as leukemia and lymphoma

All others should consider taking melatonin on a regular basis. You can order melatonin in bottles containing 1, 3 or 10 mg capsules from The Life Extension Foundation

Preventing Heart Attacks And Strokes
ASPIRIN
This is an extra added bonus to our top ten coverage of life extension drugs. Seventy-five percent of Americans die from heart attacks and strokes. There’s no point in taking all or any of the life extension drugs listed in this magazine if you’re going to drop dead of a heart attack or stroke caused by a blood clot that blocks your blood circulation before the anti-aging benefits of these drugs take effect.

Even if you don’t die immediately from a stroke, you stand an excellent chance of becoming partially or completely brain dead. If you don’t suffer from a stroke, transient ischemic attacks (TIAs) can cause chronic loss of neurological function as a result of decreased circulation to the brain.

One of the best ways of preventing heart attacks and thrombotic strokes is the daily intake of low-dose aspirin–1/4 to 1/2 an aspirin a day. Aspirin works by a mechanism that is different than anti-thrombotic nutrients, such as green tea extract, ginkgo, vitamin C, vitamin E, folic acid, etc. The nutrient that most resembles aspirin’s anti-clotting action is EPA/DHA fish oil supplements. We highly recommend fish oil supplements for a wide range of health benefits, but most People do not like the “repeating” that occurs after ingesting fish oil capsules and fish oil capsules are fairly expensive.

Alternative medicine practitioners are often biased against aspirin because of the side effects that chronic over-dosing of aspirin can produce. Two regular aspirin tablets contain 650 mg of salicylic acid and people in chronic pain have been known to consume 4-to-12 regular aspirin tablets a day and consequently suffer serious side effects. A baby aspirin tablet has only 81 mg of aspirin, which is all you need to protect you against heart attacks and strokes, and if you take it with a heavy meal, there is little risk of gastric irritation.

Aspirin is just too inexpensive and readily available for life extensionists not to take. Aspirin reduces overall cardiovascular disease risk, may lower colon cancer risk, and Durk Pearson and Sandy Shaw have uncovered evidence of a unique mechanism by which aspirin may slow the decline in protein synthesis during aging.

The Life Extension Foundation sells a fund-raising aspirin product called Healthprin. Each tiny heart-shaped tablet contains just 81 mg of aspirin, equal to just one-quarter of a regular aspirin tablet. Healthprin heart-shaped aspirin tablets are easy to break in half if you only want to consume only 40 mg of aspirin a day.

Anti-ageing pill proven in patient trials

New York: Backed by over 2,000 clinical studies — including the American Medical Association, Stanford University, and New York Academy of Sciences — 25AGAIN™ Improves Sex Drive, Energy, Lean Muscle, Fat Loss, Bone Density, Skin Moisture, Anxiety, and Depression.

In a dramatic medical breakthrough, 25AGAIN™ Anti-Aging Pill has been proven to quickly reverse the aging process by replenishing the body’s own production of Youth Hormone to normal 25-year-old levels. Youth Hormone, or DHEA, is the most dominant and plentiful hormone in the body, produced continuously by the adrenal glands. It declines rapidly after age 25, causing the onset of the aging process – impotence, fatigue, flabby muscles, abdominal fat, osteoporosis, dry skin, memory loss, anxiety, and depression.

Extensive medical research — over 2,000 clinical studies in the past 10 years, summarized at www.25again.com – documents that the bodyÂ’s Youth Hormone releases over 50 essential anti-aging hormones, including testosterone in men and estrogen in women, that control the anti-aging functions of the body and maintain youthful physical and mental health.

After age 25, the body’s own production of Youth Hormone declines dramatically. At age 40, the level falls to only 60% of normal. At age 55, the level drops to 40%, and by age 70, we make only 20% of normal. 25AGAIN™ restores the level to 100% within days.

“As an aging baby boomer, I refuse to grow old gracefully,” states Wayne Josephson, 55, president. “25AGAIN™ has literally changed my life. The results were immediate. Within days, my mood improved, anxiety disappeared, and my sleep was deep and restful. After a week, I had more energy and handled stress more calmly. After two weeks, my sex drive increased. After a month, I began losing abdominal fat, muscle mass increased, and my skin was no longer dry. I have used 25AGAIN™ for over a year, and I certainly don’t look or feel my age.”

Stress

Stressful situations release the hormone dehydroepiandrosterone-S (DHEA-S) in the body which helps us look and feel younger, as well as boosting sex drive and improving memory. Those who produce more of the hormone are better able to deal with stress.

DHEA-S is produced by the adrenal glands in response to stressful situations. It assists brain and body function, boosts memory and mood and keeps skin supple, weight down as well as boosting libido. Like other hormones production decreases as we age.

Ultimately it is the way that we deal with stress that has the potential to allows stress to become a negative or positive force in our lives.

For example, when we find ourselves in a threatening situation, our heart beats faster and our muscles tense. This is known as the fight or flight response and our ancestors depended on this reaction for their survival – to escape enemies and predators. We still use it today but in lesser situations and the body returns to normal.

It is constant stress when the body does not return to normal that can result exhaustion and illness. In life crises such as bereavement, marriage breakdown or depression, doctors have found that the immune system becomes impaired and the
body manufactures large quantities of stress chemicals particularly corisol. At the same the activity of “natural killer” (NK) cells, which circulate in the blood ready to attack foreign bodies and mutant cells are supressed.

These are some of the symptoms of long-term stress:

* Fast and shallow breathing
* A racing heart which can led to chest pains, tingling, palpitations and asthma
* A dry mouth
* Muscle tension and pain.
* High blood pressure
* Nausea, indigestion, heartburn and ulcers.
* Sweating
* Sudden feelings of fear and panic
* Feelingtense, nervous or wound-up
* Difficulty getting to sleep, staying asleep, or waking
early
* Constant feelings tha something awful might happen
* Feeling irritable, edgy and bad-tempered
* Irregular eating patterns and often eat too much or too little
* Smoking or drinking too much, or take tranquillisers or other drugs
* Suffering from upset stomachs, diarrhoea or constipation
* Difficulty with concentration, memory or making decisions
* Constantly feeling exhausted
* Worrying that you will lose control, crack up or become ill
* Feeling apathetic – like nothing matters
* Feeling short of breath even when resting
* A feeling of tightness in the neck, chest or head
* Avoiding worrying situations
* Unable to turn off certain worrying thoughts
* A loss of interest in sex
* A sensation of palpitations or butterflies in the stomach or chest
* A lack of self-confidence
* Constant worrying that you will not be able to cope
* Frequent headaches
* Feeling thatlife is not worth living
* Feeling pessimistic about the future
* Feelingunder strain.
* Feeling obsessive about certain issues
* Constant aches and pains that worry you
* Feeling very emotional and crying easily
* Feeling physically run down
* Feeling dizzy, remote, unreal or faint.
* Can’t be bothered to see friends or take up interests

What can you do about stress?

Although there is no magic cure or pill to cure stress, there are certain lifestyle changesthat will help you better cope with it and diminish its impact on your health and life.

Look after your health by eating foods that help you to be fitter and strengthen your immune system. There are also mood-enhancing foods that trigger the release of the serotonin which has a soothing effect – these include vegetables and
wholegrains. Vegetables contain high levels of the amino-scid L-Tryptophan which is also a serotonin trigger.

Take more exercise. Go for a 15-minute run before work. Don’t eat lunch at your office desk – go and sit in the park and take a walk. Take the dog for a walk before dinner.

Do something to make you laugh.

Develop a positive attitude.

Express your feelings

Learn to delegate

Relax and take time out for yourself

If you do feel stressed breath deeply and slowly, close your eyes and go to a place where you feel good – like a palm-fringed beach, where you can listen to gentle waves lapping back and forth. Practice this several times a day and it will help you relax and refocus.

There are a number of alternative therapies that can help with stress such as massage, acupuncture, aromatherapy, flotation and Bach Flower Remedies. Read about these in more detail in Alternative Therapies

About Elixir

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Avril O’Connor is the Editor of Elixir News and Elixir magazine. It has been developed from a passion which began in 2002 when there was a proliferation of web sites selling anti-ageing products and services….but few with an independent voice.

In April 2005 Elixir News was born. It is editorially independent enabling consumers to better make informed choices about their health and anti-ageing products and services.

We do not accept payment to write endorsements of products and services or for the inclusion of experts and services in our directories. This enables Elixir News to be a credible and independent news source, as well as including all the services and professional experts that we consider relevant to our readership. Nevertheless inclusion is not an endorsement by us and should it come to our attention that any business mentioned on our site is being conducted in an illegal or unethical manner we will remove it from our directories.

Visitors to our site should also bear in mind that many claims are made for anti-ageing products and services that are not necessarily substantiated by scientific evidence and should always take the expert advice of a qualified medical doctor.

It is the intention of Elixir News to fairly report and investigate the facts. If we consider that any claims for products/services are bogus or unsubstantiated we will say so. If you have had negative experiences with businesses in this sector please let us know and we will take up the challenge. We also report on our positive experiences with products and services. Advertising or sponsorship is clearly labelled as such.

We hope that you will find our web site useful in arming you with knowledge that can help you live a longer and happier life. But once again we do advise anyone with persistent health problems to consult a qualified medical practitioner/doctor. Anyone embarking on a intensive anti-ageing programme should, in particular, seek the advice of a qualified specialist about the supplements they plan to take and in what quantities, as they may conflict with drug therapy and certain medical conditions. The doctor may advise certain blood and other tests to determine your individual needs.

Please do let us know about your experiences and feedback on the information within this site. Email us at info@elixirnews.com