By David Jay Brown
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 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
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
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
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.
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
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 on van Vollenhoven's work. This study is
supposed to show whether or not DHEA has value in lupus. They haven't reported
the results yet, but the rumor is that the results are very promising,
confirming what the Stanford group has shown.
So here you have a hormone that
somehow or other puts a damper on auto-immunity. We know that if you're
chronically ill with rheumatoid arthritis, your DHEA values are very low.
Infection also puts a stress on DHEA levels. Hans Selye, the father of the
concept of stress as a factor in survival and behavior, found that DHEA was the
most potent hormone for protecting his animal models against stress-related
injury. So the idea, then, is not to take a pharmacologic dose of DHEA that will
suppress your endogenous (produced from within a cell or organ) production
dramatically, but to take a dose to replace what will bring you back to age
twenty. In other words, the physiological amount that was present at the most
youthful, reproductive phase of your life, which is age twenty.
David: Is there evidence that taking
DHEA as a supplement suppresses endogenous production?
Dr. Regelson: Well, I don't know.
But the assumption might be that it would. So. I think you need to be aware of
David: What guidelines would you
offer to someone interested in trying DHEA as a therapeutic agent?
Dr. Regelson: I think it would be
good to have a baseline level of your own DHEA done. It's always good if you
have a doctor who's supportive of you ? although most doctors are not
cooperative (because it's not FDA
approved) and they don't read, and
they don't pay any attention. So, you need to find a good doctor, who's
interested in it, and supports you taking it as a replacement. I take it every
other day rather than every day to avoid getting major storage in my body fat,
or to avoid suppressing my own endogenous production. So I pulse it (emulating
the body's natural pulsatile release of DHEA). I don't know whether this is
valid or not because the studies have not been done.
David: What's been your personal
subjective experience with it?
Dr. Regelson: I can't judge that, as
I've been on it for seventeen years. My wife's been on it for about twenty-one
years now, and she does not suffer from osteoporosis.
Labrie's group from Montreal has
found that DHEA can be substituted for estrogen and progesterone in
post-menopausal women. It's been available in Europe as Prasterone® for at least
twenty years as a post-menopausal hormone replacement therapy. So it's not that
we have to worry about its toxicology. It's a very benign hormone. If you take
too much, women will get a little extra hair on their face or maybe some acne.
If you cut the dose, it goes away.
David: Are those the only side
Dr. Regelson: As far as we can tell.
David: If DHEA is the precursor to
all these other steroid hormones, why would somebody want to take other steroid
hormones with DHEA?
Dr. Regelson: Why should one take
others simultaneously? I don't know. It would depend on whether DHEA can act to
fully maintain the other hormone levels. I don't know that there's enough
information to give us absolute answers on that. But if you read Labrie, the
suggestion is that it can do that.
David: Is there any evidence that
the body loses some of it's ability to break DHEA down into the other steroid
hormones, such as testosterone andestrogen?
Dr. Regelson: Not to my knowledge.
But there may be variations in ability among different individuals. According to
Labrie it's certainly an excellent anti-menopausal hormone for maintenance of
bone integrity. There are claims that DHEA can improve mood and energy
performance in aging individuals . Although, some people are raising questions
about the work being done at the University of California, La Jolla, who are
making these positive claims. Some people claim that the data isn't strong
enough. However, there is very good data that DHEA is a very good
antidepressant, that it can improve mood. So does testosterone. It may very well
work by increasing the endogenous level of male hormone, which makes you feel
There are also reports that DHEA and
pregnenolone (the precursor to DHEA) can relieve depression. They
reverse it. Lithium reverses depression, prozac reverses depression, but here we
have native hormones that are reversing it. A group from St. Louis has really
solid data on this with pregnenolone, and Wolkowitz at the University of
California at San Francisco has found that DHEA is effective for treating
depression in the elderly. He is giving DHEA to an elderly population, carrying
out a very good study to see if DHEA can effect dementia. This is an area that
has not yet been proven, by itself, to have any long lasting value. But on a
theoretical basis it might have some value. Additionally, there's evidence that
DHEA can effect platelet aggregation, preventing platelets from clumping to form
DHEA also lowers blood cholesterol
dramatically. I think this should really be examined and used for the treatment
of diabetes ? for both adult-onset and juvenile diabetes. This is because DHEA
enhances the action of insulin. Also, as mentioned earlier, juvenile diabetes
may be due to a sensitivity to the Coxsackie-B-entero virus which can be
prevented with DHEA, however in mice. Unfortunately I don't know of anybody
who's really doing a good human study.
David: I wasn't aware that juvenile
diabetes is caused by a virus that attacks the pancreas.
Dr. Regelson: One of the concepts
about why some people get juvenile diabetes is that their islet cells (insulin
secretory cells of the pancreas) get wiped out. You see,
there's an irony here, because most people think that islet cells beget islet
cells, so that if you've wiped out your islet cells you've had it. But that's
not necessarily true.
See, there are two cell populations
in the pancreas. There's the acinar cells, which are the digestive secretory
cells of the pancreas, and then there are the islet cells which give rise to
insulin. And everybody thinks that insulin cells give rise to insulin cells. No,
it's the acinar stem cells that give rise to the insulin-making islet cells. The
islet cells are made by the asinar cells. So it's wrong to assume that because
you have no islet cells you've had it. It's theoretically possible that the
islet cells could come back from acinar stem cells of the pancreas that are
involved in digestion.
One of the potential values of DHEA
is that if it can block auto-immunity in the case of lupus, perhaps it could
block auto-immunity in regard to acinar cell sensitivity in juvenile diabetes.
One of the concepts is that juvenile diabetes may be due to a virus, and that
may stimulate an autoimmune reaction. In other words, you come down with the
virus, and you react to it in the cell, and then you now have an autoimmune
The concept is that the Coxsackie
virus sets up an autoimmune disease. But how do you explain, if you've come down
with a Coxsackie virus infection, why you permanently wind up with juvenile
diabetes? Does that mean that you've wiped out every islet cell, and they'll
never come back? That's kind of absurd, I think. You see, what I think you've
done is every time a new generation of islet cells attempts to come from the
acinar stem cells they get wiped out. But it isn't as if you may not be able to
regenerate them. That's my concept. Now, I don't know whether I'm right or not,
as it's not my field. But it strikes me as being very logical, and there are
occasional diabetes patients that have been treated with DHEA who have shown
improvement. But nobody's done a good, consistent study on this.
David: What are some of the latest
developments that you've made in your research with DHEA?
Dr. Regelson: I'm working with
Muhammad Kalimi (also on staff at Medical College of Virginia, Virginia
Commonwealth University), my best friend as well as my collaborator. We're
growing hippocampal cells in tissue culture. The hippocampus is a tiny little
brain nucleus that looks like a seahorse. It's involved in short-term memory and
sexual cyclicity. It's very susceptible to stress. If you stress an animal, you
knock the hell out of the hippocampus.Saperstein has shown that. So we grow
these human embryonic cells in tissue culture, and if you add glutamate, beta
amyloid, or hydrogen peroxide, you destroy these hippocampal cells in culture.
But if you throw in DHEA, pregnenolone, or estrogen, then you protect them. So
here are hormones with neuro-protective capabilities. These are all neurocrines
? they're all found in the brain ? which actually protect the hippocampus from
destruction by agents which we know damage it. In addition, the stress-mouse
model and DHEA has a profound effect on protecting the animal from stress. It's
a two-hour experiment in which the mouse's movement is restricted. This is a
real stress to a mouse. It causes muscle wasting and stress-related death of the
animal. By giving them DHEA they are protected.
David: What are some of the future
directions that you see for research in this area?
Dr. Regelson: I think that one of
the researchers who's really done some of the best work in relation to pointing
the way to mechanisms where DHEA is valuable is Raymond A. Daynes' work at the
University of Utah. Daynes has shown that DHEA affects IL-6,
corticosteroid-mediated cytokine, which is a stress-mediating factor. This
factor also promotes the growth of certain tumors, and DHEA inhibits the
production of this stress factor. So it has an anti-stress effect. It can also
have anti-tumor activity and has value in septic shock (inadequate blood
circulation due to pathogenic microorganisms in the blood). DHEA also protects
mice from wasting from stress. Stress causes sarcopenin (muscle-wasting), and we
can prevent that with DHEA. More work has to be done in these areas.
The person I'm working with now, who
I'd like to see succeed, is Tim Cochran of the Cochran Foundation. He has a
poly-pharmacy (multiple drug therapy) preparation of DHEA and
other hormones, etc. with which he's treating congestive heart failure. He also
is treating Parkinson's Disease, and this is a very promising area. The problem
is it's poly-pharmacy, so people don't take it seriously. But I think he's made
a major breakthrough.
Then you have Henry Lardy, at the
University of Wisconsin, who has come out with his own derivative of DHEA ?
which he's patented ? and is now trying to market. What Lardy has shown is that
DHEA can protect mitochondria, which are important for each cell's energy
system. In the final analysis, we're only as young as our cell's energy system.
So if you can maintain the integrity of mitochondria, you can maintain the
quality of survival.
DHEA can protect the mitochondria of
the energy systems, and your youthful state is dependent on how you use energy.
Aging occurs when you can't utilize energy to maintain the integrity and repair
capacity in the cell. That's basically what aging is. So I think the final
common pathway that relates to aging is our ability to maintain our
mitochondrial cell energetics-- those are the little furnaces in the cell that
provide us with the ability to burn food, and turn it into energy. There's
evidence that DHEA can protect mitochondria, and that may be the final common
pathway that is vital to aging.
I'm not concerned with the length of
life, so much, as I am with the quality of survival. I mean, I'm not a
Kevorkian. What I mean to say is that life for life's sake has no meaning,
unless there's quality to it. That's the fundamental problem that we're faced
with in our society, which we're only just beginning to do something about. At
my university the administration is acting in a very stupid fashion. I want to
develop a successful aging program that will appeal to the baby boomers, so that
we can develop a program of bio-quantification, and rational intervention.
Unfortunately it's moving very slowly. But that university which starts programs
of this kind will make it in a very big way, both economically and socially.
What we want to do is prevent people being debilitated and dependent.
I'm currently 73, and I know what my
future is, unless I can do something about it. But I'm concerned with the
quality of my survival, not necessarily the length of my survival. I want to be
productive, and physically and sexually active until the day that I die. That's
what I want. I want to go like James Whitcomb Riley's "Wonderful One-Horse
Shay". I want to fall apart-- boom-- once, and not hang on to life. I don't want
to be crippled and dependent in the process if I can avoid it. And that's what
our direction should be-- how do we keep animals alive and healthy? And that's
where hormone replacement comes in.
That 's the whole concept of my book
The Super-Hormone Promise. The promise is in our replacing hormones that decline
with aging, to reproduce the reproductive state, that period of our life where
we're most physically fit, and most active. I think that really is my
fundamental philosophy that has to do with embracing aging. Unfortunately
gerontology has gotten a bad name. It's nursing homes, and elder-hostile, and
putting a patchwork on problems that already exist.
What we have to do is prevent these
problems from developing, because our society can't afford to develop an aging
society that's debilitated. Who's going to pay for it? We have to change our way
of thinking. I mean, we have enough information that indicates there's certain
things that can be done. For example, if you could prevent osteoporosis in
women, you can avoid 200,000 hip fractures a year.
We need to find a way to maintain
people so that they're functional until the very end of their lives. This
doesn't necessarily mean that they're working, but that they're taking advantage
of life in the full sense of the word. I mean, look what's happening now. People
in their seventies are still youthful. It's when you get into the upper
seventies, and the eighties, that you start seeing this severe debility in our
The potential for DHEA is hormone
replacement. We shouldn't be saying "Oh my God, we don't know anything about it,
and it may do this." Fortunately, right now, we have Gene Labs and van
Vollenhoven's group, which are studying it in lupus, and they're doing a good
double-blind study. They're being secretive about their data, because they want
to meet FDA requirements. But the preliminary work of van Vollenhoven's, where
he's giving DHEA at a fairly large, pharmacologic dose-- 200 milligrams a day--
shows that he's not seeing any major toxicity. And his patients are improving.
It's a safe hormone. We have to learn to use it.
I resigned from the local lupus
society because we have about fifteen doctors in the Richmond community that are
rheumatologists who deal with lupus, and not one of them is giving DHEA. I don't
deal with this patient population. So I sent out a memo, and I said read the
literature. I sent them copies of van Vollenhoven's paper, and I said start
treating your lupus patients with DHEA. But nobody listens. They're waiting for
an FDA clearance, which is still a couple of years away. In the meantime, people
are dying of lupus and coricosteroid toxicity. People should read and do
something about it. That's why we have to go beyond lupus, and see what it does
for other autoimmune diseases, including maybe asthma.
DHEA, incidentally, will suppress
mastis sarcomas, which are mass-cell tumors. We've shown this and reported it.
The mass cells play a major role in autoimmune reactivity, particularly in
regard to asthma, and cutaneous allergy. DHEA suppresses that mass cell. So
people have to start looking. The trouble is that the action on the part of the
National Institute on Aging is very slow. They're finally beginning to put out
research requests, and people are beginning to get money to do the work. But, I
think, they're ten years behind the times because they're so slow and
conservative. If a drug company could see it as a profit-making enterprise, it
would have moved a long time ago. I tried to get Hoffmann-La Roch interested it
twenty years ago, but they said they couldn't patent it, so they weren't
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Dehydroepiandrosterone (DHEA) the multifunctional steroid: II. Effects on the
CNS, cell proliferation, metabolic and vascular, clinical and other effects.
Mechanism of action? Ann NY Acad Sci. 1994;719:564-575.
2. Loria RM, Inge TH, Cook SS,
Szakal AK, Regelson W. Protection against acute lethal viral infections with the
native steroid dehydroepiandrosterone (DHEA). J Med Virol. 1988;26:301-314.
3. van Vollenhoven RF, Morabito LM,
Engleman EG, McGuire JL. Treatment of systemic lupus erythematosus with
dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol.
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formation of androgens and estrogens in peripheral target tissues: its role
during aging. Steroids 1998;63:322-328.
5. Daynes RA, Araneo BA, Ershler WB,
Maloney C, Li GZ, Ryu SY. Altered regulation of IL-6 production with normal
aging. Possible linkage to the age-associated decline in dehydroepiandrosterone
and its sulfated derivative. J Immunol. 1993;150:5219-5230