DHEA and Glucose Metabolism
Investigators have shown that DHEA inhibits Glucose–6–Phosphate Dehydrogenase (G6PDH), an enzyme that breaks down glucose. There are two glucose–metabolizing pathways in the body, the catabolic, energy–yielding pathway and the anabolic, biosynthetic pathway. G6PDH happens to be the first enzyme in the biosynthetic pathway, the one which results in the synthesis of fatty acids and ribose (the sugar used in making deoxyribonucleic acid, or DNA). In simple language, G6PDH turns glucose into fat.

DHEA’s inhibition of G6PDH may redirect glucose from anabolic fat–production into catabolic energy metabolism, thus creating a leaner metabolism. This function of Dehydroepiandrosterone is well reviewed by Arthur Schwartz and colleagues in their chapter on “The Biological Significance of Dehydroepiandrosterone” in The Biologic Role of Dehydroepiandrosterone. They assert that DHEA–mediated reductions in Ribose–5–Phosphate activity may be centrally responsible for the anti–tumor promoting, anti–tumor initiating, and possibly the anti–atherogenic properties of DHEA. They also note that DHEA 1) produces hepatomegaly (liver enlargement), 2) stimulates liver catalyses activity (a protective antioxidant enzyme), and 3) causes proliferation of peroxisomes (cellular organelles which specialize in oxidative processing and the decomposition of hydrogen peroxide). The absence of such influences with synthetic analogs of DHEA (like 16–alpha – fluoro – 5 – androsten – 17 – one) prompts Schwartz and colleagues to recommend that such analogs be considered for clinical applications in humans. Toxicity factors still need to be assessed.

DHEA and Appetite
In different experiments, Dehydroepiandrosterone supplementation has resulted in increased, decreased and unchanged food consumption. Dr. Schwartz found that it is the level of dietary fat influences food consumption. DHEA–treated rats on a high–fat diet ate less food than control rats while those on a low–fat diet ate more.

Since DHEA inhibits G6PDH activity and suppresses the body’s ability to synthesize fat from carbohydrate, dietary sources of fat become more important. This can affect changes in appetite. But despite possible increases in food intake, DHEA–treated animals consistently weighed less than control animals. In other words, increases in appetite, when indulged, did not negate the anti–obesity property of DHEA.

DHEA and Aging
The body’s production of Dehydroepiandrosterone drops from about 30 mg at age 20 to less than 6 mg per day at age 80. According to Dr. William Regelson of the Medical College of Virginia, DHEA is “One of the best biochemical bio–markers for chronological age”. In some people, DHEA levels decline 95% during their lifetime – the largest decline of an important biochemical yet documented. In animal studies, Dehydroepiandrosterone extends rodent life spans up to 50%. The animals not only lived longer, they looked younger. The graying, course–haired controls could easily be distinguished from the sleek, black–haired, DHEA–treated animals.

DHEA levels are directly related to mortality (the probability of dying) in humans. In a 12–year study of over 240 men aged 50 to 79 years, researchers found that DHEA levels were inversely correlated with mortality, both from heart disease and from all causes. This finding suggests that DHEA level measurements can become a standard diagnostic predictor of disease, mortality and lifespan. Furthermore, if animal results hold true, supplemental DHEA may prevent disease, reduce mortality, and extend lifespan in humans.

Enhancing Brain Function
DHEA may also be intimately involved in protecting brain neurons from senility–associated degenerative conditions, like Alzheimer’s disease. Not only do neuronal degenerative conditions occur most frequently when DHEA levels are lowest, but brain tissue contains many times more DHEA than is found in the bloodstream. One of the scientists at the forefront of this field of research is Dr. Eugene Roberts who found that very low concentrations of Dehydroepiandrosterone were found to “Increase the number of neurons, their ability to establish contacts, and their differentiation” in cell cultures. He also found that Dehydroepiandrosterone also enhanced long–term memory in mice undergoing avoidance training. It may play a similar role in human brain function.

Drs. Roberts and Fitten report initial research on “Serum steroid levels in two old men with Alzheimer’s disease before, during and after oral administration of DHEA” in the book “The Biologic Role of Dehydroepiandrosterone”. Roberts’ and Fitten’s data are the best we’ve seen regarding acute and chronic changes in numerous hormone levels following various oral doses of Dehydroepiandrosterone (see adjacent graphs). Because of the short peak duration of Dehydroepiandrosterone (heavier line in illustration), they recommend that future studies or therapeutic trials use time–release capsules or transdermal patches to provide more uniform delivery of DHEA.

DHEA and Immune Function
DHEA is known to enhance general immune response. Oral and subcutaneous DHEA has been observed to protect rodents against the lethality of RNA and DNA viruses, and lethal bacterial infections. Dr Loria, Regelson and Padgett report in “The Biologic Role of Dehydroepiandrosterone”, that a single subcutaneous dose of Dehydroepiandrosterone is considerably more effective in protecting against infection than oral dosing. Intraperitoneal [within the abdominal cavity] injections were completely ineffective.

Dr. Loria and colleagues noted that subcutaneous dosing did not result in the typical weight loss observed with oral Dehydroepiandrosterone. Presumably it works by a different mechanism. DHEA has been reported to counteract the thymic involution [shrinking of the thymus gland] and immuno–suppression caused by corticosteroids. But the special role of skin tissues in the immune facilitating properties of DHEA suggest a different mechanism is involved. Cutaneous immune cells, such as Langerhans cells and keratinocytes, are believed to play a role in “Immune surveillance” and “Antigen presentation”. These cells may be a site of DHEA’s action. Subcutaneous injection of DHEA results in the “Formation of a local deposit leading to a relatively prolonged exposure to the lymphoid system”. Dehydroepiandrosterone skin patches might provide a similar exposure.

Neither DHEA nor androstenediol have any direct (in vitro) antiviral activity. The amount of viral load in heart, spleen, pancreas, liver and blood tissues was unaffected by either Dehydroepiandrosterone or androstenediol administration. The effect of these steroids appears to be strictly mediated through stimulation of lymphocytes, lymphoid organs, and immune–modulating cytokines [immune hormones].