John Asarian, M.D., M.P.H. and Marcia Zimmerman, M.Ed., C.N.

Dehydroepiandosterone (DHEA)

DHEA is your most abundant steroid hormone, a powerful antioxidant and is considered a cancer deterrent by leading researchers. DHEA is produced primarily by the adrenal glands and to a lesser extent by the central nervous system. Your body converts DHEA into DHEA-S which is its active form. DHEA-S is in turn converted into testosterone and other androgens (androstenedione, androsterone), and estradiol and other estrogens.  DHEA secretion is regulated by the hypothalamic-pituitary axis (HPA). Another pituitary hormone, adrenocorticotropic hormone or ACTH, activates the release of DHEA. As one ages, there is reduced responsiveness to ACTH which results in a decline of DHEA that parallels the decline in HGH.  DHEA shows dramatic cycles of high and low points throughout life. It is high at birth, drops dramatically until puberty and then rises sharply into adulthood. Thereafter, it declines progressively with age. Analysis of serum levels has shown that there is a 25 percent decline in DHEA each decade until age seventy, when levels are negligible. By age sixty-five, levels are only 10 percent to 20 percent of those at age twenty to twenty-five. Perhaps the most significant effect of this decline is in the brain where DHEA levels are five to six times greater than in any other body tissue. As levels of DHEA fall in the rest of the body, the human brain appears to maintain fairly consistent levels, presumably from DHEA production within the brain itself . Other degenerative changes associated with aging in humans such as atherosclerosis and lowered immune function are believed to be the result of diminishing DHEA levels.

What's particularly puzzling to scientists is that DHEA levels fall dramatically as one ages while other adrenal hormones such as cortisol remain relatively stable.  Another puzzling fact is that people of the same age can have vastly different levels of DHEA. While one may have very low levels, another person of the same age will have much higher levels. Moreover, an inverse correlation seems to exist between serum DHEA levels and the IGF-1 insulin hormone system, in that those who are obese, have insulin resistance, hypertension or diabetes, often have the lowest levels of DHEA.

Here is a summary of the actions of DHEA and how DHEA supplements may be useful in overcoming some of the symptoms of aging:

• may increase immune resistance against infection
• increased life expectancy has been demonstrated in laboratory animals
• appears to reduce the risk of many age-related conditions such as coronary artery disease, cancer, osteoporosis
• possible help in the prevention of adult-onset diabetes mellitus
• helps in weight-loss and improvement in ratio of lean muscle to fat, possibly by raising testosterone levels with a subsequent increase in lean body mass

Studies show a 20 percent decrease in cardiovascular disease mortality in men having high levels compared to those with low levels

Two excellent recent well-controlled studies demonstrated significant increases in IGF-1 levels in those supplemented with DHEA-perhaps by stimulating the liver to produce more IGF-1 or by the generation of more HGH receptors. Dosage used was 50 mg. daily.

Low doses, (50 mg. to 100 mg for men and 25 mg. to 50 mg. for women), depending on age, appear to raise DHEA levels to those aged twenty to thirty.

A study of men between the ages of sixty and eighty showed that those with the highest levels of DHEA were the most fit, tested younger and leaner and had higher testosterone levels that those with the lowest DHEA levels. The effect of DHEA on prostate cancer or benign prostatic hypertrophy isn't clear at the present time. Studies indicate that DHEA supplementation does not increase the risk and may in fact help prevent it. There is also good evidence from a study done at Stanford University that it helps in the treatment of systemic lupus. Another study showed that relaxation techniques decreased the stress hormone cortisol level and increased DHEA levels. Relaxation techniques have been suggested by anti-aging experts such as Dr. Klatz, to be as effective in raising HGH levels. 

Some cautions are in order in the use of DHEA supplements. You should avoid DHEA supplements if you have ovarian or prostate cancer, or other hormonally dependent cancers. If too much is taken while the body is still producing adequate levels, you may dampen or turn off the body's production. Extremely high doses of 1600 mg in men have been reported to cause feminizing effects. Androgenic effects in women such as appearance of facial hair, have been observed when dosages between 100 mg. and 1600 mg. were taken. There have also been some reports of lowering of helpful HDL cholesterol levels in those taking DHEA. Women who have high cholesterol or low HDL should not take DHEA. Two cases of heart arrhythmias have also been reported.

Other Hormones Associated with Aging

Progesterone

Progesterone is produced in the adrenal glands of both men and women, and also in the ovaries and testes. Progesterone is the primary hormonal precursor of male and female sex hormones and the adrenal steroid, cortisol. Progesterone is one of two major female hormones produced in the ovaries - the other being estrogen. In females, the balance between these two hormones is critical to sexual function. Estrogen levels rise during the first half or follicular phase of the menstrual cycle. Following ovulation at mid-cycle, estrogen levels taper off and progesterone levels rise sharply. In many women the second, or luteal phase, is disrupted when the surge in progesterone doesn't occur. A common treatment for PMS has been a prescription of progesterone.

About twenty-five years ago, a Petaluma, California physician named John Lee, M.D. found that a natural progesterone preparation could be effectively administered through a cream applied to various parts of the body. Progesterone cream has shown remarkable results in alleviating PMS, particularly breast tenderness, water retention and mood swings. Dr. Lee cites other benefits for both men and women using progesterone cream. Included are increased alertness and energy, anti-inflammatory activity, normalizing blood pressure and restoring normal libido. Many of these symptoms, not surprisingly, are associated with menopause and progesterone cream has relieved these symptoms in addition to relieving hot flashes, skin dryness, loss of water under the skin, and bone thinning. The icing on the cake, according to D. Lee is that in years of using progesterone cream, he has seen no side effects in any of his patients, nor have they been reported by other physicians.

Estrogen

Estrogen can also cause a great deal of mischief. Nearly every organ in the body, including the brain, has estrogen receptors.  When estrogen binds to these receptors, several bi ochemical events are initiated, all important to survival of the species. However, excess amounts of estrogen can flood the receptors and over stimulate the tissues, causing undesirable effects and even cancer. Scientists have discovered that soy foods and a few other plants produce estrogen mimics called phytoestrogens. Soy phytoestrogens are weak estrogens that bind to receptors and effectively prevent estrogen from binding. The excess estrogen is then conjugated in the liver and eliminated from the body without causing harm. The Food and Drug Administration recommends the amount of soy protein needed to reduce risk of coronary heart disease is 6.25 grams.

It has been determined that soy protein can supply enough phytoestrogens to prevent several aging conditions including heart disease, osteoporosis, menopause symptoms and possibly prostate cancer.

The decline in hormone levels contributes to all aspects of aging, loss of muscle, water content of tissues, fragile bones, thinning hair, and decreased vision and hearing. Another remarkable effect of aging is on our brain and nervous system, including a general reduction in our feeling of well-being. Even insomnia can be traced to lowered levels of hormones. These are the "neuro-" effects of the neuroendocrine theory of aging.

The Brain Connection - Another Aspect of Neuroendocrine Aging

Earlier we talked about the role of the hypothalamus in stimulating the pituitary to release growth hormone. The hypothalamus conducts an entire orchestra of activities that coordinate the body's immune, hormonal, and nervous systems. The connection between the brain and all of these systems is so significant, a whole new area of science has emerged - psychoneuroimmunology or PNI. The brain, along with the systems it governs, goes through the aging process. As we get older, we become more forgetful, may find it more difficult to learn new things and have less ability to adapt to stressful situations. On the psychological level, we are less comfortable with change and more inclined to worry and fret over the small stuff.

We can offset many of these difficulties by addressing the specific nutritional needs of the brain and nervous system. Nutritional strategy includes:

• improving circulation and delivery of nutrients to the brain
• providing the necessary vitamins and minerals to activate brain cells
• increasing the stress adaptive capacity of the brain
• supplying the amino acid precursors for specific brain chemicals including neurotransmitters and neuropeptides

As we age, blood vessels all over the body and especially the tiny capillaries in the brain become less flexible and often become narrowed due to plaque build-up. Consequently, they are less able to provide oxygen to meet the great energy demands of the brain. They are also not able to deliver as many nutrients to brain cells. Since the brain is the most energy demanding organ of the body, the result of impaired blood flow is reduced brain function including memory, stress adaptation and learning capacity.

Another important factor in brain function are levels of specific brain chemicals known as neurotransmitters and neuropeptides. These protein-like substances are the messengers that carry information between the ten billion or so brain cells and between the brain and nerves. The primary neurotransmitters are serotonin, dopamine, gamma amino butyric acid or GABA, glutamic acid, acetylcholine, and norepinephrine. Neuropeptides are protein-like brain stimulants including somatostatin which controls release of growth hormone, vasopressin that affects memory, ACTH that causes release of cortisol, angiotensin II that controls vascular pressure, substance P and enkephalin that control pain and many others with numerous effects throughout the body. Now, let's take a look at what specific nutrients can affect brain function.

Ginkgo biloba

Ginkgo biloba is an herb that has been widely used for improving memory in Japan and other countries over many centuries. These are the well-documented functions of ginkgo:

• improvement in the ability to tolerate low oxygen supply
• increased memory performance and learning capacity;
• protection against free radical damage to the brain, including reperfusion injury and oxidative stress;
• relaxing blood vessels in spastic conditions, which may be mediated through increased nitric oxide production, a potent vasodilator;
• may enhance catecholamine and other neurotransmitter release;
• in humans, ginkgo has also been observed to reduce platelet aggregation.

Clinical Uses for Ginkgo

Ginkgo has proven useful in several clinical settings including the treatment of mild to moderate dementia of the Alzheimer's type. Controlled studies with the standardized extract (25% ginkgo flavonglycosides and 6 % terpenes) have shown significant improvement. Ginkgo tends to slow the progression of these conditions by about six to twelve months (Le Bars et al JAMA, 1997) The senior editor of JAMA, Margaret Winkler, M.D. commented that "Few treatments for Alzheimer's disease (AD) have been found to be both effective and acceptable to patients and their care givers."

A 1999 review of ginkgo used for several types of dementia revealed that a majority of randomized controlled trials supported the conclusion that GBE was "efficacious in delaying the clinical deterioration of patients with dementia or in bringing about symptomatic improvement." (Ernst and Pittler, 1999). Some other improvements seen in patients include improved circulation in the legs of those with peripheral occlusive arterial disease and a small but significant increase in pain-free walking distance in these patients. There are some secondary clinical uses for ginkgo. These include:

• improvement in short term memory
• improvement in sexual function in men and women who had diminished sex drive and performance as a result of anti-depressant use (Cohen and Bartlik, 1998).
• macular degeneration
• prevention of altitude sickness
• vertigo and tinnitus (ringing in the ears)

In addition to its usefulness, ginkgo has proven very safe to use, with less than 2 per cent incidence of minor side effects, including headache, nausea, and other gastrointestinal symptoms. Four cases of bleeding have been reported due to ginkgo's anti-clotting effects. There have also been some reports of allergic skin reactions. It should not be used by those who are pregnant or lactating.

Siberian Ginseng

Stress adaptation is an important aspect of brain aging to address. Siberian ginseng has been used in Russia for many centuries as an "adaptogenic" agent. This means that it helps keep you on an "even keel." When you are tired, it helps you feel energized, yet when you are over-stimulated, it calms you down. Siberian ginseng is one of the safest and most useful herbs for assisting in relief of stress and adapting to stressful situations. Several B-vitamins are needed to assist in stress management. Those especially important for the brain are niacin, vitamins B-6 and B-12 and folic acid. The mineral magnesium is extremely important in energy production in the brain and zinc is required to stabilize the membranes of brain cells. Calcium, sodium and potassium all play vital roles in neurotransmission. And, speaking of neurotransmitters, using precursor amino acids is effective in improving neurotransmitter function. The most important are L-glutamine and L-tyrosine that are precursors of the neurotransmitters and neuropeptides mentioned earlier. Now, let's move onto the next theory of aging.

WEAR AND TEAR THEORY

Collagen is the most plentiful protein in the body. It makes up all of our structural components, skin, blood vessel walls and linings of organs, digestive and respiratory tract, and body cavities. Structurally, collagen is very strong and consists of intertwining strands of protein that have bridges interconnecting the strands. Vitamin C is necessary for collagen production and there is considerable evidence that pycnogenols bind to the bridges between collagen strands, further stabilizing them. Aging collagen begins to fray and lose its elasticity. It falls prey to free radical attack, particularly on the skin surface. Cross-links are formed between the protein strands so they become less resilient, wrinkle and crack. OPCs may help diminish the cross-linking that occurs within your body. The appearance of your skin may change, with some reduction in wrinkling because of the action of OPCs.

Joint Wear and Tear

Collagen is the protein that makes up cartilage - the tough, slippery substance that allows bones to glide smoothly past one another. Cartilage also has remarkable cushioning properties that act like shock absorbers. Cartilage is also an extremely moist material with 65 to 80 percent of it being a watery substance called proteoglycans. Wear and tear eventually takes it toll on the cartilage found in the body's highly mobile joints known as synovial joints. These joints are found in elbows, knees, hips, hands, feet, fingers and toes. The joints come in many sizes and shapes but they all have structures in common. These are the joint capsule that holds the bones together, the synovium or inner lining of the joint, cartilage which caps the ends of the bones and absorbs shock, ligaments that attach bones together and tendons that attach muscles to bones.  Additionally, the joint is cushioned by synovial fluid that is secreted by the synovium. Some joints such as those in the elbow and shoulders also have fluid filled sacs called bursa. As we get older, these parts begin to wear out, so that by the age of fifty, nearly everyone has some signs of osteoarthritis. It may be confined to morning stiffness or may involve severe pain and swelling in several joints. We get stiffer as we age in part because collagen protein that makes up joint structures loses some of its resiliency, but also because our joints literally "dry out." The cushioning fluid is reduced, leaving the synovium covering the ends of bones rubbing against one another as they move. Eventually, these protective joint linings become worn and pitted. We may even begin to hear clicking and grinding as we move.

Glucosamine

Glucosamine is an integral component of a group of lubricating and cushioning materials known as glycosaminoglycans or GAGS.  This group includes hyaluronic acid, chondroitin sulfates, and keratan, heparin and dermatan sulfates. GAGs attach to proteins such as cartilage to form proteoglycans, which was mentioned in the above paragraph. Our bodies manufacture glucosamine from glucose and glutamine and then attach it to complex sugars to form GAGs. Glucosamine is sometimes referred to as an "amino sugar" because it is composed of a sugar and an amino acid.  When we are younger, we can manufacture enough of this material from dietary sugars and proteins. As we get older, it may be necessary to supply these molecules as a dietary supplement. According to Jason Theodosakis, M.D., "this natural substance stimulates the production of and serves as the raw material for the water loving proteoglycans (GAGs) that bind water in the cartilage matrix." Oral glucosamine is well absorbed and the body utilizes it to build new cushioning material and fluids in joints. Several forms of glucosamine are available, including glucosamine sulfate, glucosamine hydrochloride and N-acetyl glucosamine. All of these glucosamine forms are suitable precursors for regenerating cartilage. Although glucosamine does not alleviate pain directly, it has demonstrated anti-inflammatory properties that may result in reduction in joint pain. Most of the evidence for its effectiveness comes from the glucosamine sulfate form. However, glucosamine hydrochloride and N-acetyl glucosamine appear to be equally effective. Nearly all glucosamine salts are produced by processing crustacean shells.

Chondroitin Sulfate

Chondroitin sulfate is one of the GAGs mentioned above. GAGs are also referred to as "mucopolysaccharides" because they are sticky, slimy sugars - just what is needed to lubricate joints. Chondroitin and glucosamine have slightly different roles but seem to work best in combination. As one ages, the amount of chondroitin sulfate in cartilage diminishes whereas the amount of keratan sulfate and hyaluronic acid increases. These changes are thought to contribute to the development of osteoarthritis. Dr. Theodosakis suggests in his most recent book, Maximizing the Arthritis Cure, that these two natural supplements:

• increase the production of proteoglycans, GAGs, and other key elements of healthy cartilage;
• enhance the manufacture of hyaluronate which makes joint fluid viscous and able to lubricate joints;
• slow the enzymes that needlessly break down cartilage or interfere with the flow of nutrients;
• help clean up cholesterol, fibrin, fats and other deposits in joints and nearby blood vessels;
• reduce pain.
• improve mobility.

Most chondroitin is produced from calf trachea, although New Zealand green-lipped mussels and oysters are good dietary sources. Green-lipped mussels have been concentrated into dietary supplements, as well. Whale or bovine cartilage has also been used to produce chondroitin. Dr. Theodosakis recommends supplements that supply 500 mg of glucosamine to be taken three times a day (1500 mg total) and 400 mg of chondroitin to be taken three times per day (1200 mg total). These must be taken on a continuous basis for at least three months. He has found a 90 percent response rate if patients follow his entire regime which includes the supplements boron, calcium, chromium, copper, magnesium, manganese, selenium, zinc and low dose silicon and extra vitamin D if not included in the diet or other supplements. Some questions have been raised about the quality and purity of glucosamine products. Dr. Theodosakis warns against purchasing products that are much lower in cost than competitors. They may be impure or contain very little chondroitin, the more expensive of the two ingredients.

OBESITY THEORY

It has been well established in the scientific literature that carrying extra pounds increases your biological age. The heavier you are, the older your biological age. Obesity also correlates with increased prevalence of cancer, heart disease, kidney disease, mental deterioration, and diabetes. Over eating as you get older is especially harmful, particularly if weight gain occurs in the mid-section of your body. Waist to hip ratio is a good indicator of your risk of heart disease. If you are a woman and your waist measurement is 1.8 times greater than your hip measurement, you are at high risk. For a man, the greatest risk is 1.1 or greater.

According to Roy Walford, M.D., a leading proponent of limiting one's caloric intake as an anti-aging strategy, the more nutritious your diet, the fewer calories it takes to satisfy you. He advocates eating only wholesome foods such as fruit, hot cereals, skim milk, soups, salads, pasta, fish, chicken, brown rice, vegetables, and whole wheat toast and rolls. Dr. Walford advised against eating eggs, whole milk, steak and refined foods such as bacon, juice, buttered white toast, fast and fried foods, steak, buttered vegetables, cake and ice cream. Most adults, according to Dr. Walford, can maintain ideal weight by consuming between 1800 and 2200 calories per day.

If you are overweight, it may be helpful to "jump start" your system with a good weight loss and cleansing program. Such a program can help overcome the cravings you may have, help your body eliminate toxins and help you naturally desire more wholesome foods. §

References
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Authors Biographies

Dr.John Asarian has been a practicing physician for over twenty-six years. He has a growing interest in anti-aging medicine, especially the role of antioxidants in the prevention of chronic conditions. In addition to his California clinical practice he is an experienced network marketer and graduate of the MLMUniversity Coach Training Program. Dr. Asarian is the physician leader in Oasis, where he heads a large national organization of professionals. He has led trainings throughout California and in the Midwest on leadership, building successful home-based businesses, anti-aging and nutritional supplements.

Marcia Zimmerman is a nutritional biochemist, teacher and a former researcher at Stanford University School of Medicine. Ms. Zimmerman is a top trainer for nutritionists and co-author of a nutrition certification program. She has written over sixty nutrition articles and two landmark books, THE ADD NUTRITION SOLUTION-A Drug-Free 30-Day Plan and EAT YOUR COLORS! Maximize Your Health by Eating the Right Foods for Your Body Type. Ms. Zimmerman has changed the lives of thousands of people in the U.S., Canada, Europe, and Asia with her innovative nutrition programs and supplement formulas and she is a well-known media personality. Marcia has been a nutrition expert for many leading nutritional and pharmaceutical companies.

Email: zgroup@pacbell.net

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