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William Regelson

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 this caution.

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 effects?

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 good.

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 blood clots.

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 reaction.

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

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