Adequate levels of GSH are required for several aspects of the immune response, including mixed lymphocyte reactions, T-cell proliferation, T- and B-cell differentiation, cytotoxic T-cell activity, and natural killer cell activity. Substances used to replenish GSH, and there are several, counteract oxidative stress and inhibit HIV transcription and replication in models of acute and latent HIV infection.

Lowered levels of glutathione lead to immune cell dysfunction in multiple ways, and allow body cells and tissues to become damaged from oxidative stress.

Insufficient glutathione also means that the liver is less able to properly break down drugs and other toxins, increasing the potential for liver damage from HIV meds. Thus, boosting glutathione levels is important for anyone living with HIV.

It is particularly crucial for those coinfected with hepatitis C since researchers have shown that glutathione levels in both the blood and the cells are significantly depressed in people with hepatitis C, and that oxidative stress is clearly tied to both the grade of liver fibrosis and the level of liver cell damage. In addition, a lack of all the needed nutrient building blocks may prevent the proper daily repair and maintenance of all the body’s organs, including the liver and kidneys, heightening the risk of med-induced damage.

Because HIV is a chronic condition (one that can be treated butnot cured), the body is in a continual state of response to the infection, and thus is constantly generating damaging free radicals. Putting out this “fire” by “quenching” free radicals, in turn, has the result of using up glutathione inside cells. Studies have documented dramatic deficiencies of glutathione in people with HIV.

If agents like glutathione are depleted, there is nothing to stop the free radicals from causing damage. The way they do this is to set off a chain reaction with a whole string of consequences. A superoxide or reactive hydroxyl molecule will bounce around (so to speak) and give off it’s “hot potato” electron to the nearest available molecule. That molecule won’t want this hot potato either, and will try to pass it off. Meanwhile, it may have sustained damage to its structure--which might mean damage to the DNA, the cell membrane, or other organelles like mitochondria. But with the right antioxidants around, this damage can be stopped.

To understand how this damaging process is thwarted, picture the following chain of events. When an antioxidant, or reduced form of a chemical, “quenches” a free radical, it becomes oxidized, setting off a cycle of chemical reactions. The antioxidant can “handle” that hot potato. The chain might start with vitamin E donating an electron to a lipid peroxide. This prevents that lipid peroxide from damaging cellular fats, like those found in membranes. However, the vitamin E is now “oxidized” and needs an electron. Vitamin C can provide that, and regenerates the E. Glutathione may also regenerate vitamin E from its oxidized to reduced form. But now the vitamin C is oxidized. Alpha lipoic acid can reduce the oxidized vitamin C (as well as glutathione and CoQ10).

Then the oxidized glutathione (GSSG) must be returned to a reduced state (GSH). GSSG is reduced to GSH done by NADPH. Now the NADPH has become NADP and it needs to be reduced. This is done by oxidizing glucose-6-phosphate (G6P) to 6- phosphogluconolactone. Get the idea? This is an exquisitely bound set of reactions, a well-oiled machine as it were.

But this is all the more difficult when it is being used up in the chronic fight against the inflammatory effects of HIV or chronic viral hepatitis. (Or, one might add, from smoking.) Not to mention that the body is losing all that sulfur in the form of cysteine—which is one of the principle ingredients of glutathione!

Conclusion: restoring and maintaining GSH levels in HIV/AIDS (and Hepatitis C) is essential for restoring vital vitamin C and E antioxidant action, protecting cells/organs against oxidative damage, and slowing or stopping chronic intracellular viral activation. By restoring and maintaining levels of GSH, you may help restore cellular immune responsiveness and improve immune function overall. The best way to do this is using a range of nutrients, which is one of the reasons using a multivitamin makes sense.

Glutathione has also been shown in laboratory conditions to either dramatically inhibit active viruses, including HIV and herpes viruses, or stop the reactivation of virus inside quiescent (quiet) cells.

Because of the high amino acid glutamate levels in HIV infection, various forms of cysteine are actually blocked from being used by immune cells and therefore a mixture of different sulfur amino acids (thiols), along with GSH itself, is thought to be the wisest course of action in attempting to re-supply glutathione. High levels of glutamate block some cells’ ability to import cysteine for producing more glutathione. (This is why we don’t think long-term use of very high dose glutamine is a good idea, since it is readily transformed into glutamate. This is certainly an area for clinical research.)

About the absorption of oral glutathione: While oral consumption of GSH gets into cells along the GI tract, it seems very unlikely that it gets further (like in blood plasma). Results of studies are mixed. Some show (in animal models) a blood plasma half-life that is very short (about 2 minutes!) Others clearly show increases in both intestinal epithelial cells and even in plasma when taken orally (as opposed to by injection).

The good news is that studies of N-Acetyl-Cysteine (NAC), whey protein powders, and alpha lipoic acid as a supplementation regimen have shown a good impact on restoring and maintaining GSH levels. To understand how these supplements affect glutathione levels in the body, please continue on to the sections on NAC, whey protein, and alpha lipoic acid found below.

Glutathione Reduced Capsules (Jarrow) Each bottle, 60 capsules. Each capsule, 500 mg. Some research suggests that the most effective dose is 15 mg per kilogram (2.2 lb) of body weight. Thus, 2-3 capsules is good for a 150 lb person.

Take GSH on an empty stomach, 20 minutes before or 90 minutes after eating. Again, PWHIV find that the best time to take this is the first thing in the morning when they get up.

Some researchers are investigating dosages of 3 grams per day (or 12 capsules per day). These data were never published, suggesting they failed to find evidence of absorption into the bloodstream. One study of dietary intake of glutathione (which is found in cooked meats like chicken as well as in cooked asparagus, fresh oranges, raw carrots and some other foods) showed that it appears to get into the intestinal tract epithelial cells—which is perhaps where it is most needed (see Methods in Enzymology, 1995;252:3-13). However, there are no data as of early 2005 to suggest that glutathione taken orally will go beyond the GI tract. We just don’t know. But it seems it may be worth a try, although it is not inexpensive. Alternatives like NAC, alpha lipoic acid and whey make sense.

Dr. Wulf Droge, one of the researchers who discovered GSH deficiency in the 1980s, released a research report suggesting that AIDS can be viewed partly as the result of a virally-induced cysteine deficiency. This observation arises from studying GSH levels in several primate (monkey) models who do not proceed to immune suppression after being infected with HIV. He discovered that these monkeys, unlike similarly infected humans, never lose the substantial amounts of GSH and sulfur (thiols) within their blood or their immune cells. Subsequent research in humans underscores the effects of this loss of sulfur and glutathione and its relationship to disease progression.

Droge and his group have noted a massive loss of sulfur in people with AIDS, largely as a result of the depletion of the glutathione pool and cysteine loss. The observed global sulfur (thiol) deficiency stimulates HIV replication, accelerating disease progression. The loss of this critical group of sulfur amino acids, mainly cysteine, interferes with the host defense system since there is nothing to mop up all the free radicals generated in the battle against HIV. Thus, there is considerable “collateral damage” to healthy cells and tissues, particularly in the gastrointestinal (GI) tract.

WebMD.com: Glutathione: New Supplement on the Block