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Life Extension Magazine

LE Magazine March 2003

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The Death of Anti-Aging Supplements?

In 1513, at the age of 53, Juan Ponce de Leon began earnestly searching for the fountain of youth-a mythical spring fabled to possess the ability to restore health and vitality to all who bathed in its waters. Now, almost five centuries later, scientists continuing that ill-fated Spanish explorer's quest for youth may actually have found it-in the human body.

After decades of painstaking work, researchers worldwide have finally begun to unravel the mysteries surrounding the aging process. DHEA, one of the human body's most abundant hormones, has been proven not only to decline in direct proportion to aging, but also to be a major component in maintaining health and vitality. In just this past year alone, researchers have discovered that DHEA at increased levels effectively reduces the risk of heart disease, promotes brain cell growth and survival, reduces the symptoms of depression, lupus and arthritis and, perhaps most stunning of all, is an effective chemopreventative agent against cancer!

But all of that work may come to nothing if Congress has its way. A new Bill introduced in October would seriously undermine the legitimate usage of certain over-the-counter anti-aging supplements, including DHEA. Known as H.R. 207 or the "Anti-Andro Bill," this legislation is designed to curtail the usage of certain muscle-building "andro" supplements by teenagers. The scope of H.R. 207, however, is so broadly written that it includes DHEA and other beneficial anti-aging supplements. This Bill could be interpreted to make DHEA a controlled substance, the possession of which is punishable under the Federal Controlled Substances Act of 1970. Although the Bill is not without its merits-such as keeping ignorant teens from abusing steroid hormone precursors-its myopic restrictions may result in incalculable harm to the nation's older citizens.

It appears that regardless of the valiant strides medical science has taken in its quest to overcome debilitating age-related disorders, and bring hope to millions of older Americans, the fountain of youth may be lost forever.

The following article provides a brief update on new findings about DHEA published over the past twelve months. In it, we examine some of the latest groundbreaking research that has propelled DHEA into the forefront of the anti-aging industry. (For more information about H.R. 207 and to find out what you can do to stop it, read the article titled "Anti-Aging Supplements May Soon Be Illegal!" in this issue.)

Since initially isolated by Nobel Prize winning biochemist Dr. Adolf Butenandt in 1931, dehydro-epiandrosterone, commonly known as DHEA, has been a controversial medical enigma whose anti-aging properties are as compelling as they are elusive.

Arguably one of the most popular and potentially effective anti-aging supplements, DHEA has recently become the subject of intense debate and scientific scrutiny, resulting in a surge of research whose goal has been to reveal-or refute-the life saving potential of this biomarker of aging.

DHEA: Biomarker of aging

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DHEA and its sulfated metabolite, DHEA-S, are the most abundant circulating hormones in the human body.1 Nicknamed the "mother hormone," DHEA is actually a prohormone-a neurosteroidal progenitor produced by the adrenal cortex, gonads and central nervous system (CNS)-whose offspring are converted into over 50 essential hormones including testosterone, estrogen and cortisone.2 DHEA's ability to provide life-sustaining hormones is one reason why it is so critical to healthy metabolic functioning in aging humans.
As we age, the endogenous level of DHEA is drastically reduced. Research has shown that optimal production is between the ages of 20 to 25, with each successive decade seeing diminished levels-dropping down to as low as 20% by the age of 70.3 Numerous studies have also indicated that this decrease in DHEA is directly associated with many age-related disorders including immune dysfunction, autoimmune disease, heart disease, mental disturbances, osteoporosis and blood sugar instability. These established correlations suggests that high levels of DHEA may be associated both with longevity and vitality.

Neurological benefits

As a partial product of the central nervous system, DHEA is especially abundant in the human brain.4 Consequently, many studies have reported that DHEA provides an appreciable level of defense against many of the neurodegenerative diseases commonly associated with advanced age. Alzheimer's patients, for example, have shown substantially lower levels of DHEA in comparison to healthy subjects as well as an associated reduction of blood flow to the hippocampus-the area of the brain believed to be associated with memory.5 Prior studies have also demonstrated that DHEA is a significant factor in restricting the damage associated with stroke, and is equally instrumental at lowering the autoimmune response during brain injury-thereby reducing the inflammation and protecting nearby healthy neurons.6 Evidence now suggests that in addition to having neuroprotective characteristics, DHEA may also be directly related to neurogenesis -the formation of new neurons.

A group working at the University of Cambridge has determined that treating rats with subcutaneous DHEA pellets actually increased the number of newly formed cells in the dentate gyrus of the hippocampus. Most notable, however, was the fact that the neurogenesis effect was especially prominent in older rats. These results prove that DHEA effectively regulates neurogenesis in the hippocampus and modulates the inhibitory effects of increased corticoids on both the formation of new neurons and their survival.7

The relationship between diabetes, a blood sugar disorder that often results in neural damage, and levels of circulating DHEA was recently a topic of study by doctors at the Diabetes Endocrinology Research Center and Department of Internal Medicine in Iowa. According to their findings, nutritional supplementation with DHEA may be a candidate for treating diabetes-induced vascular and neural dysfunction.

In their study, they found that supplementing the diet of streptozotocin-induced diabetic rats with 0.1%, 0.25%, or 0.5% DHEA caused a dose-dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment-factors that are decreased in diabetes. They also determined that at 0.25%, DHEA significantly improved both vascular relaxation and sciatic nerve enzyme activity, and prevented oxidative stress damage inherent to diabetes. This suggests that at moderate dosage, DHEA is effective at treating both vascular and neural dysfunctions associated with diabetes.8

DHEA also shows promise in protecting against Alzheimer's disease. An article recently published in the Journal of Clinical Endocrinology and Metabolism described researchers' attempts to investigate the significance of neurosteroids in Alzheimer's disease.

The study focused on the individual brain regions of Alzheimer's disease (AD) patients, including hippocampus, amygdala, frontal cortex, striatum, hypothalamus and cerebellum, and found that a general trend toward decreased levels of all steroids was observed in all AD patients' brain regions compared with controls. The results concluded that pregnenolone sulfate (PREGS) and DHEA-S were significantly lower in the striatum and cerebellum, and that DHEA-S was also significantly reduced in the hypothalamus. The study further found that high levels of key proteins implicated in the formation of plaques were correlated with decreased brain levels of DHEA-S, suggesting it has a possible neuroprotective role in AD.9

Depression, cognitive abilities and DHEA

Depression is a common condition associated with aging. Often misconstrued as sadness or grief, depression is characterized by a lowered mood, feelings of worthlessness, difficulty concentrating and various somatic disorders.10 Far from simply being the result of neurotransmitter dysfunction, depression can be symptomatic of a variety of illnesses including degenerative disorders that damage vital neural tissue. Consequently, DHEA's role as an anti-depressant has been rigorously examined for years.

During these many trials, researchers routinely found that when taken daily, DHEA supplements effectively reduced depressive episodes and enhanced mood. In fact, according to one major study in the UK, as many as 67% of men and 82% of women reported a noticeable decrease in their depressive symptoms while taking as little as 25 mg/day of DHEA.11 In addition, women suffering from adrenal insufficiency have reported an improved sense of well-being and an associated increase in both sexual interest and sexual satisfaction while taking DHEA.12

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More recently, researchers at the University of Newcastle Upon Tyne, UK tested DHEA to see if it offered any protection against cortisol, a glucocorticoid known to be elevated in patients with depression.

In their study, cortisol and DHEA were measured in saliva taken from 39 patients with unipolar depression who had been medication free for at least six weeks. These samples were then compared with those of 41 non-depressed subjects. The results showed that the level of cortisol was significantly higher than that of DHEA in the depressed patients when compared to healthy subjects. This indicates that reduced DHEA levels may be a marker for depressive illness and a contributing factor to the associated deficits in learning and memory. These results also suggest that the administration of DHEA or other anti-glucocorticoid treatments may reduce neurocognitive deficits in major depression.13

To further correlate the association of DHEA with depression, researchers from the Center for Torture and Trauma Survivors in Sweden examined the levels of DHEA-S in refugees suffering from post traumatic stress disorder (PTSD). According to their results, DHEA-S was observed to be higher in non-depressed PTSD cases than in non-PTSD without depression, suggesting an interaction between PTSD, depression and levels of DHEA-S.14

Although research into DHEA's ability to promote improved cognitive functioning in humans is still mired in the early stages of development, scientists at Open University, UK demonstrated that it does have the potential to increase memory retention. Their studies found that by administering intracerebral injections of DHEA and DHEA-S 15 minutes before or up to 60 minutes after training, one-day-old chicks showed enhanced recall ability for up to 24 hours. These findings provide evidence that neurosteroids such as DHEA and DHEA-S have memory-enhancing properties and may constitute therapeutic tools for the treatment of cognitive deficits.15

Continued on Page 2 of 2

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