AIDS HIV and DHEA

DHEA and HIV/AIDS

DHEA is up there with melatonin as the miracle supplement of the moment. Available at health food stores, DHEA has been touted as an anti-aging supplement and potential treatment for lupus, multiple sclerosis, and AIDS. Since it is marketed as a food supplement, DHEA escapes the usual FDA testing requirement for drugs. DHEA (dehydroepiandrosterone) is a naturally occurring precursor of both androgenic and estrogenic steroids. It is synthesized largely by the adrenal gland. In men and women, blood levels of DHEA peak at age 20 and decrease thereafter. The few studies exploring the benefits of DHEA provide reasons to be hopeful, but they can only be considered preliminary. Furthermore, virtually all had a small number of participants. The best were summarized in a recent issue of The Medical Letter (11 October 1996), a physician publication without drug advertising.

Reduces Viral Load

At last summer's International Conference on AIDS in Vancouver, ateam of researchers reported a study of 20 HIV-infected people who had never taken antiretroviral drugs. DHEA, 300 mg or 600 mg twicedaily, produced reductions in viral load. (No placebos were given.) In a three-month study of 28 people with systemic lupus, 200 mg DHEA daily produced symptom improvements not shown among the people taking placebos. In a study of people with multiple sclerosis given DHEA (no placebos), they reported increased feelings of strength, stamina, and well-being, but no reduction in disability. In another study, men over age 50 with high blood levels of DHEA also had lower rates of heart disease. The same study showed no benefit to women.

Anti-Aging

The anti-aging claims for DHEA probably stem from the few preliminary studies of healthy older people. Forty healthy people, aged 40 to 70 years, were given 50 mg of DHEA daily or a placebo in a study that lasted six months. No benefit was noted by those taking placebos, but the majority on DHEA reported improvements in psychological and physical well-being.

A 12-month study of 16 men and women taking 100 mg of DHEA daily produced similar results. As with any new drug, the side effects profile for DHEA is yet to be fully understood. The Medical Letter warns of DHEA's potential for androgenic effects in women, such as acne, hair loss, hirsutism (excessive body and facial hair), and deepening of the voice. (Hirsutism and voice changes may be irreversible.) In men, DHEA holds the possibility of stimulating the growth of prostate cancer. Despite early indications of potential benefit, The Medical Letter comes to a negative conclusion: There is no convincing evidence that DHEA has any beneficial effect on aging or any disease. Patients would be well advised not to take it. The FDA hasn't received much in the way of bad news about DHEA, though the supplement has been on the market for years. Only a few reports have come in on DHEA, and none were severe, said a spokesman for the FDA's Center for Food Safety and Applied Nutrition.

"DHEA had a major effect on my sexual performance."

Howard Wasserman of Los Angeles read about DHEA last year and, at age sixty-eight, figured it was worth a try. "If I could do anything to retard the aging process, I'd be very happy to do it," he says. Although Wasserman has high energy levels, he was feeling the inevitable effects of aging. He had also had three back surgeries since the late 1980's. So a physician prescribed DHEA for him--he takes 50 mg a day--and he's found that he copes better with various day-to-day stresses. "It has not had any effect on my libido, but it did have a major effect on my [sexual] performance," Wasserman says. "It's like I'm thirty-five years old." Taking supplements, his blood levels of DHEA are comparable to those of a young man. Wasserman gets a PSA test every six months to assess his risk of prostate cancer, and the tests have shown that he's at very low risk for prostate cancer. Wasserman feels that the DHAE has helped speed his recovery from the third back surgery. "If you saw how I hop and jump around, you would never believe I've had three back surgeries," he says. HealthFacts, Nov 1996

"We're in limbo," says Varro Tyler, one of the country's foremost herb experts and author of The Honest Herbal. On the one hand, he says, some unethical companies are making outrageous claims for inferior products, and the law makes it difficult for the FDA to do anything about it. On the other hand, the few restrictions on the books force responsible companies to word their labels so vaguely they're useless, even misleading. The only guarantee is confusion. When it comes to the public's health, there's been a long tug-of-war between individual liberty and regulation. For most of the country's history, liberty had the upper hand. In 1937, however, a poisonous elixir killed more than 100 people, and the regulators began to gain ground. At first the FDA merely required manufacturers to prove that a drug was reasonably safe. Then a wary official in 1962 refused to approve a sedative called thalidomide. In Europe, where the drug was widely available, thousands of babies were born with terrible limb deformities after their mothers took the drug during pregnancy. Having averted disaster here, the agency went a step further and began to require large well-controlled trials to prove prescription drugs safe and effective.

The FDA also decided to reappraise all previously approved drugs to see if they worked as claimed. Of the many herbs on the list, only a handful made the cut. Most others could still be sold, but manufacturers couldn't claim they would treat a disease or condition. That loophole left the FDA uneasy. Finally, in 1993, the agency proposed that many herbs, and any vitamins sold in dosages exceeding 150 percent of the recommended daily allowance, should be considered prescription drugs. To many health-conscious baby boomers, it was a call to arms. "If I were FDA commissioner," Tyler says, "I would take the 25 to 50 best-proven herbs in the world and approve them as over-the-counter drugs. I would set up a blue-ribbon panel of experts to review the evidence and then set about expanding the list." Tyler models his suggestions on Germany's widely respected Commission E. In 1978 that commission began reviewing all the available literature -- whether scientific or anecdotal -- on more than 300 herbs, eventually approving two-thirds. The United States, he says, should adopt the German standard for sanctioning herbs as drugs: absolute proof of safety and reasonable proof of efficacy. ....In other words, for the foreseeable future you'll have to fend for yourself. Read labels skeptically, avoid kitchen-sink herbal cocktails, and look for standardized extracts. If you have a serious condition or take prescription drugs, discuss any supplements with your doctor. (Pregnant women should be particularly careful; many supplements pose risks to the fetus.) If you buy herbs regularly, pick up a well-researched guide, or call the American Botanical Council, at 512/331-8868, to order pamphlets on specific herbs.

DHEA

The fortunes of DHEA and melatonin have risen and fallen in near parallel. Sometimes called the mother hormone because the body converts it into estrogen and testosterone, DHEA iS secreted by the adrenal gland. Fifty years of research have suggested the hormone might alleviate everything from impotence to cancer, heart disease, and the autoimmune disease lupus. Like melatonin, however, DHEA grew popular as an antiaging remedy; and as with melatonin, the most dramatic evidence comes from studies on mice. At the University of Utah School of Medicine, for instance, immunologist Raymond Daynes has seen a "clear 100 percent change" in mice given a DHEA compound, with twice as many animals on the hormone surviving two years. William Regelson once again trumpeted the benefits of supplements, this time in his book The Super-Hormone Promise. Among DHEA'S powers, Regelson declared, is the ability to lower the risk of cancer. But a month after the Journal of the American Medical Association threw cold water on the melatonin craze, a companion essay declared the verdict still out on DHEA as well; because it raises the levels of sex hormones, the journal noted, it might increase a person's odds of developing ovarian, prostate, and other kinds of cancer. Again, the operative word is might: Neither the benefits nor the risks have been proven. (When it comes to more superficial concerns, however, a few are clearly grounded in fact. High doses of DHEA can increase facial hair in women.)

Serum cortisol/DHEA ratio & HIV

According to an abstract submitted by the authors to the Ninth Symposium on HIV Infection entitled From Virology ... To Therapy, held March 6-8, 1997, in Toulon, France, "The progression of HIV infection is accompanied by a severe immunodepression due predominantly to the selective depletion of CD4 lymphocytes, particularly during advanced stages. The adrenal steroid hormones, especially cortisol and DHEA, modulate the immune system. Cortisol decreases T-cell proliferation and function, inhibiting the production of cytokines. The adrenal androgen DHEA stimulates helper T-cell function, enhancing the capacity of activated T cells to produce interleukin-2, and counteract inhibition of this important Lymphokine by the glucocorticoid. We therefore studied the serum concentrations of cortisol and DHEA and their cor- relations with the absolute CD4 cell counts in HIV positive men. The results of our five retrospective and prospective studies indicate that the serum con- centrations of cortisol and DHEA in HIV infected patients are different from those of HIV negative controls. Serum cortisol is elevated at all stages of infection (+20 to +50%, p<0.05 to p<0.001) particularly in AIDS patients (stages IV C). In contrast, the serum DHEA concentrations are closely corre- lated with the stage of HIV infection. Serum DHEA is higher in the early stages (stages II and III or >500

CD4) of disease than in advanced stages (IV C or <500 CD4), or incontrols (+40 to 100%, p<0.01 to p<0.001), and below normal instages IV C. There was a negative linear correlation between CD4 cellcounts and cortisol (r=-0.4, p<0.02) and a positive linear correlation withDHEA (r=+0.36, p<0.01). These results show that there is a linkbetween the circulating concentrations of adrenal steroids and theprogression of immune suppression during HIV infection. High serumDHEA could enhance the T-cell function to offset the immunodepressioncharacteristic of HIV infection and/or induced by elevated cortisol. The drop in serum DHEA associated with increased serum cortisol in AIDS patients may trigger an immunodepresssion (the decrease in CD4 cells). This raises the question of whether there is a cause-and-effect relationship between clinical progression and the ratio of serum cortisol and DHEA concentrations. Further investigations into the relationship between the cortisol/DHEA couple and both immune response and nutritional status should indicate the exact position of these steroids in the etiology of HIV infection and provide a sound basis for the developmentof new therapeutic strategies."

AIDS Weekly Plus, April 28, 1997 COPYRIGHT 1997 Charles W Henderson "Serum Cortisol/DHEA Ratio During HIV Infection." N. Christeff, S.Gharak- hanian, and E.A. Nunez. Laboratoire de Biochimie Endocrinienne et Biochimie B, Faculte de Medecine et Hopital X. Bichat, Paris; Service des Maladies Infec- tieuses du Pr. W. Rozenbaum, Hopital Rothschild, Paris, France.