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William Regelson

DHEA Update

with Dr. William Regelson

William Regelson, M.D., a practicing oncologist and research scientist, is an expert on the therapeutic benefits of hormone replacement and has been a leading researcher in the field of aging for over twenty years. He is the co-author of the best-selling books, The Melatonin Miracle and The Super-Hormone Promise, which detail the latest research in hormone supplementation and which provide intelligent guidelines for taking steps to slow and, in some cases, even reverse the aging process.

Dr. Regelson is a professor of Medicine at the Medical College of Virginia Commonwealth University and is a specialist in medical oncology. He has joint appointments in microbiology and biomedical engineering.

I spoke with Dr. Regelson about his work with DHEA and other hormones with regard to the aging process. I found him to be a very warm and thoughtful man. At 73 years of age he sounds vibrant and his mind is very sharp — a living and vital testament to his own research.

 

David: Why did you become interested in researching the therapeutic benefits of DHEA?

Dr. Regelson: It’s a bio-marker for aging and it declines in a linear fashion with the progression of aging. If you’re going to approach aging rationally, you have to bio-quantitate human aging. DHEA, as a bio-marker for aging, is one of the best indicators of how old you really are. It has been proven valuable in the prevention of cancer. So, I clinically studied it as an anti-tumor agent. I gave it to about 20 patients with a variety of cancers. We also used it to treat people with multiple sclerosis because it has anti-viral activity as well.

David: Was this study written up? What were the results?

Dr. Regelson: Yes, we wrote it up in The Biologic Role of Dehydroepiandrosterone (DHEA), which is a book that we published in 1990 by Walter de Gruyter. We mention it in the text. We didn’t write it up as a definitive paper, because the results were negative. Well, they weren’t completely negative. We had an MS paper that came out, which appeared in our book, along with a MS paper by Eugene Roberts (from the City of Hope in Duarte, California) using DHEA.

Roberts gave a gram a day, and we gave forty milligrams per kilogram per day. And patients with MS did feel stronger. They did lose heat intolerance, and showed improvement. But remember, both of us had only about twenty patients per study, and it wasn’t a double-blinded study, so there was no way to develop comparison. One had to go on the basis of individual evaluation, and numbers where small. We couldn’t stimulate anybody in the field to do it. I think DHEA is worth trying with multiple sclerosis.

As far as cancer is concerned, unfortunately the numbers were small. It was a pilot study, and, again, I couldn’t stimulate interest. At the time that we did it, I ran into political trouble here at the medical school in regard to the director of the cancer center, and had to drop out of cancer research, so I couldn’t pursue it. DHEA, I think, has anti-tumor activity, but it’s best as a drug in combination with other anti-cancer treatment. You can say that, that’s fine, but it’s something that has to be looked at.

There are individual reports of it improving cancer. There’s a pancreatic cancer case report I know of. There are reports of multiple myeloma, where DHEA blocks IL-6, and IL-6 is a cytokine which is involved in the stimulation of multiple myeloma. So it has a place. It just needs more work, and it needs good controlled studies, which have not been done, because it hasn’t been picked up. It’s also been looked at in breast cancer, where the results are indifferent, but again the study was not a good one.

Roger Loria and I showed that DHEA can inhibit Coxsackie-B-entero virus, which, we think, is the virus that causes diabetes in human beings. We found that it had tremendous protective effects in test animals against a variety of lethal infectious agents, particularly viral agents. So, as a result of DHEA having both anti-cancer and even cancer prevention activity, we were very interested in it.

Arthur Schwartz of Temple University School of Medicine, Philadelphia did most of the work when it comes to cancer prevention. He is really the patriarch of my interest because he’s the one who pointed out to me that cancer has a linear increase with age. Meaning the older we get the less DHEA we have. So it became logical to see how DHEA would effect aging patterns if it were to be taken to replace what had been lost due to aging. After having given it to cancer patients at pharmacologic dosages of 40 milligrams per Kilograms per day for periods as long as two and a half years, and also for lesser periods of time to multiple sclerosis patients, I felt it was a very safe drug.

David: Why?

Dr. Regelson: It was totally benign. No toxicity, nothing. And this was using extraordinarily high dosages. Forty milligrams per killogram is anywhere from six to eight grams a day. So we saw no major toxicity, except in women, where at that high dose you’ll get hair on their face. That’s a pharmacologic dose, which is a very large dose.

So I started looking at using it for myself, for my wife and for administering it under different clinical settings. Unfortunately, there was no interest at that time, meaning about the 1980’s at the National Institute on Aging. In those days, it was like, “So what!” There was no major interest. Now there’s a lot of interest in DHEA. Now there are all sorts of RO-1’s out for good DHEA studies. (An RO-1 is a contractual study with the National Institute of Health. They send out requests for proposals, and then assign the study to whoever comes out with the best request.)

David: Could you just talk about some of the general benefits that one could expect from using DHEA as a supplement?

Dr. Regelson: DHEA is, in a sense, a mother steroid. Pregnenolone is a grandmother steroid as it gives rise to not only DHEA but also to corticosteroids. DHEA doesn’t effect the corticosteroid pathway but gives rise to the male and female hormones, which decline with progressive age. It’s pretty evident to me, really to anybody, particularly in view of hormone replacement therapy for women during menopause, that hormone levels decline with age. Well, estrogen replacement is a valid approach.

We replace estrogen and progesterone, but what about DHEA? It certainly declines with age, so that when you’re in your eighties, you’re producing only ten to fifteen percent of what your body made in your twenties. The real decline is seen in your late forties, whether you’re male or female. So the idea would be to take enough DHEA to bring your body, if you will, back to age twenty. What possibilities might this have on your life span and quality of life in middle and older age?

Now here again, you can only operate on the basis of inference because human studies have not really been done. You cannot fully extrapolate from a mouse to a human being. Mice do not metabolize DHEA. Except for hamsters, rodents do not utilize DHEA. But if you give mice DHEA, it has profound effects on resistance to infection, and it improves memory performance. However, at the same time, if it isn’t a normal metabolite of a mouse, you can’t expect it to be implicated in mouse survival. A mouse does not make DHEA, although it is helped by it. So it teaches us about some of the mechanisms for DHEA action. But if you’re going to do an aging study in a mouse, and a mouse doesn’t normally use DHEA, it’s not really the ideal animal.

There’s a study now being done by Lane’s group at the National Institute on Aging regarding caloric restriction in primates. They’re doing this in rhesus monkeys at the University of Wisconsin and the University of Maryland. The studies have shown that if you calorically restrict monkeys, their DHEA values remain youthful. We’ve known for a long time that if you calorically restrict rodents, it delays the aging process. Now, this work is being extended to monkeys, which are primates, so they make DHEA the way that we do, which declines with age. These monkeys live about thirty or forty years, so there’s a more rapid decline relevant to their age.

So DHEA values stay up. Now, what does that mean? I mean, what is the exact significance of it? As a bio-marker it’s very meaningful, but why? What is DHEA doing? Is it helping the animal in some way to be healthier, and will it live longer? That’s the critical issue, particularly in primates that make DHEA. You can learn from an animal that makes it. So if we really want to do DHEA studies, we should look at hamsters, because they make it, but rats and mice do not. So if you’re going to study DHEA, and if it will delay aging, you want to do it in the right animal.

So that’s why we should be looking at DHEA in hamsters, although I don’t know anybody who’s done the appropriate studies. But certainly DHEA declines in human beings, so I believe that people should take it. It up-regulates immunity, and it down-regulates auto-immunity (immune reactions against the self).

Van Vollenhoven’s group at Stanford has shown that DHEA can reverse the symptoms of lupus, an autoimmune disease that attacks blood vessels. There is a company called Gene Labs, out of Redwood City, California, that has conducted a major study ‹ which they’re to be complimented for ‹ following up

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