American Foundation for AIDS Research, April 2000
Jeff Getty

With or without treatment, persons with HIV lose dangerous amounts of sulfur, say scientists at the German Cancer Research Center in Heidelberg. Wulf Dröge, a long-time oxidative stress researcher, and colleagues summarized their findings this past February issue of AIDS Research and Human Retroviruses.¹  In the first of three studies, the group measured the sulfate concentrations in the leg arteries and veins of 16 HIV-positive persons and 18 HIV-negative controls. The HIV-negative volunteers had a balance between blood and tissue sulfate, but those with HIV showed a net loss of sulfate from their tissues whether or not they were on highly active antiretroviral therapy (HAART).

The second and largest study measured plasma sulfate levels in 65 HIV-negative volunteers and 64 HIV-positive asymptomatic ones. The researchers found that persons with HIV on average had about one-third higher plasma sulfate concentrations, again regardless of treatment. The last study, comparing 19 HIV-positive volunteers to 21 HIV-negative ones, concluded that the HIV-positive patients were losing massive amounts of sulfur in their urine, and HAART did not stem this loss. A normal body each day excretes about 3 grams of cysteine (a sulfur-containing amino acid) and maintains a balance by ingesting the same amount. The German team estimated that the HIV-positive volunteers were excreting an astounding 10 grams per day, leaving a daily deficit of 7 grams.

The scientists also inferred that glutathione depletion was the source of this loss of cysteine and sulfur. Glutathione is made up of three amino acids, including cysteine. It plays a critical role in eliminating free radicals and thus protecting cells from oxidative damage.

Researchers have studied glutathione depletion intensely since the late 1980s. Little progress has been made in explaining why this deficiency occurs - or more importantly why replacing the sulfur or glutathione does not seem to be an easy answer.

Many surviving persons with HIV remember N-acetylcysteine (NAC), a popular oral supplement taken by thousands in the mid-90s. At the time, there were several anecdotal reports of NAC users experiencing increased weight and energy. A Stanford University study carried out by the laboratory of Drs. Leonard and Lenora Herzenberg noted little short-term benefit in patients taking NAC compared to patients on placebo.

One of the researchers who worked on this NAC study was Dr. Steve De Rosa, who recalled that the initial study was completed in 1995. A total of 60 patients were followed for eight weeks. Half the patients received active NAC and the other half a placebo. "The study showed that taking NAC replenished glutathione as measured in the lymph and red blood cells," he said. But the study found no changes in absolute CD4+ cell counts or HIV viral load. The observation period was too short, in De Rosa's opinion. Longer follow-up might have shown some clinical benefit. After the study was published, NAC fell into decline. However, some persons with HIV still claim that it helps them feel better.

Dr. Kathy Mulligan, a University of California San Francisco researcher who studies HIV-related metabolic abnormalities, is intrigued by the recent German findings. "I still think there is something more to learn about NAC," she said. She was critical of the German report, though. "There are a number of things that worry me about this article – 'massive loss of sulfur' sounds too alarming," she said. When asked whether or not patients should experiment with sulfur supplements, Mulligan seemed worried that the February report might spark a new treatment fad. "I definitely encourage people not to rush out and buy sulfur. The kind of sulfur that comes from taking tablets is not going to fix the problem," she remarked.

Leonard and Lenora Herzenbergs' group at Stanford still believes that NAC is going to prove itself one day. Cysteine in NAC is the logical and best way to introduce the correct type of sulfur into the body, they think. The Herzenbergs are trying to find funding for a much larger and longer study. "The problem with commonly available NAC is that no pharmaceutical company will provide money for a study since it cannot hold the patent." De Rosa commented. The Stanford researchers are working with at least one party interested in reformulating NAC in a patentable version and eventually applying for FDA approval.

Why do patients on and off HAART have "massive" sulfur loss even if their viral load is undetectable? De Rosa and others believe that we have not advanced far in our understanding of this disease. "Glutathione and sulfur are telling us that HAART is not the simple answer - merely the first step. We need to find more answers," he remarked. Dr. Mulligan agreed but noted that people taking indinavir are already getting plenty of sulfur from the drug.

While the details of sulfur depletion, its consequences and its replenishment require further studies, AIDS buyers clubs for years have been selling sulfur in the form of NAC. Most clients took 1 or 2 grams per day, although the Herzenberg study used 8 grams per day. (At the time, Dr. Dröge criticized this amount as excessive.) There are isolated, anecdotal reports that NAC prolonged the lives of late-stage AIDS patients.

Most of the buyers clubs have shut down because they lost customers to conventional pharmaceuticals and competing health food stores. NAC can still be found at health food stores, but De Rosa cautions that number of the brands may not be beneficial. He worries that certain over-the-counter NAC formulations are heavily oxidized. "Too much oxidation could cause some damage," he warned.

Reference

1.Breitkreutz R, Holm S, Pittack N, Beichert M, Babylon A, Yodoi J, Droge W ,Massive loss of sulfur in HIV infection.
    AIDS Res Hum Retroviruses2000 Feb 10;16(3):203-9       Abstract

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