Glutamania! -- Is There Anything Glutamine Doesn't Do?
It slices, it dices, it's a floor wax, it's a whipped topping -- the literature on glutamine, the body's most abundant amino acid, can put one in mind of those late night infomercials touting miracle products. Glutamine has been reported to stop diarrhea and wasting, build lean body mass and improve muscle definition, promote immune cell growth and even possibly slow progression of HIV disease.
Glutamine is known as a crucial chemical for muscles. Glutamine is also used by immune cells and enterocytes (intestinal cells) for energy, it's important to the liver, the kidney and the brain.
But unfortunately, just as in those infomercials, there is very little solid data to prove that this nutritional supplement can actually help people with HIV live longer and better lives. There are some tantalizing clues however, and since it has very few reported side effects and very little potential toxicity, many people have decided to try it, usually in combination with antioxidant supplements like betacarotene, NAC (n-acetyl cysteine), thioctic acid (alpha-lipoic acid), selenium and Vitamins C and E.
Here's the reasoning behind anti-oxidant use. In HIV, and other chronic illnesses, "free radicals" tend to build up in the bloodstream as a result of the way the immune system attacks its enemies. These nasty chemicals lack an outer electron. They damage the body by stealing electrons from healthy cells and lessen the body's ability to repair itself. One of the primary anti-oxidants needed to reduce this "oxidative stress" is a substance called glutathione. And you guessed it -- glutamine is one of its precursors, as is NAC.
Normally, nutrition provides enough antioxidants to combat this "oxidative stress" and neutralize the "free radicals." But under continuous siege by HIV, the need for anti-oxidants begins to grow beyond what a regular diet can provide. Wasting is one result -- muscle tissue is rich in glutamine. The body starts breaking down muscle to fight the "oxidative stress." Another result is a higher viral load, because HIV thrives in an environment rich in free radicals. Some nutritionists have begun to call glutamine a "conditionally essential" nutrient.
A recent study of about 100 PWAS, mostly men with less than 200 T-cells, done by Drs. Leonore and Leonard Herzenberg at Stanford University, found that glutathione levels are directly linked to survival. 85% of those who started the study with high glutathione levels survived the three-year-long study while only 18% with low levels did. It isn't known whether low glutathione levels cause or quicken disease progression or if they are a symptom of some other process -- however supplementation to increase glutathione levels in cells is increasingly popular. Glutathione is also crucial for liver health.
Some recent studies have suggested that taking glutathione itself can raise the glutathione levels in immune cells, but according to Dr. Judy Shabert of the Harvard University School of Medicine, the extra expense of doing so is unwarranted. "Glutathione is taken up by the intestines, but it's broken down by the liver, so it's really just a very expensive source of cysteine. Our research has found that glutamine really does make glutathione and it has the advantage of doing many other things."
A recent study in the Lancet, for example, reported that glutamine supplementation significantly decreased the incidence of pneumonia, and other life-threatening infections like bacteremia and septicemia, for patients with multiple traumas and who were being fed intravenously. In the study, only 17% of patients on glutamine got pneumonia, compared to 45% of the participants who were not on glutamine. 7% on glutamine contracted bacteremia, while 42% of the non-glutamine group did. Finally, 3% (one person!) of those in the glutamine group experienced sepsis, compared to 26% of the non-glutamine group.
The effect of glutamine on the gut is pretty well documented because supplementation has been found useful not only for people with HIV, but with other conditions that require intravenous feeding like severe bums and intestinal surgery.
A pilot double-blind study of glutamine for intestinal problems in PWAs did not produce statistically significant results, quite possibly because the highest dose used was only 8 grams and most researchers now recommend doses higher than 20 grains for acute problems. However, it did show a trend towards improvement in those on higher doses. Studies of people with other conditions have found that glutamine supplementation speeds recoveryand can even restore firm, healthy stools to people who have only inches (of a former 21 feet!) of intestine remaining.
Most people think the intestine is just an organ needed for the elimination of waste, but in fact, it is a crucial part of the immune system. Like people with HIV, cancer patients on chemotherapy often suffer severe diarrhea. Charles Smigelski, RD, a nutritionist and researcher at Harvard University, reports seeing a cancer chemo patient who had disabling diarrhea for six months. Within a week on glutamine, his bowel movements were normal.
Smigelski is high on glutamine and other antioxidant supplements for people with HIV. He has about I 00 HIV patients in his practice that are supplementing with glutamine and says, "Most people report that they feel better on every level. It improves their energy, it reduces diarrhea, and it's hugely useful in wasting and dealing with oxidative stress. A ton of people swear by it."
Smigelski believes that such supplementation may be able to prevent or reduce lipodystrophy ("Crix belly"), thought to be a side effect of protease inhibitors. His patients find it useful for diarrhea caused by protease inhibitors as well. "A very common experience is that someone will have protease related diarrhea. Immodium will stop the explosive diarrhea that often comes before people can get to the bathroom, but it won't firm the stools or reduce frequency. Glutamine, which I use in combination with probiotics (natural gut bacteria like acidophilus, lactobacillus, etc.), firms the stools. It really improves quality of life."
Body builders also tout glutamine because it is anabolic (builds muscles). A poster presented by Dr. Shabert at this year's International Conference on AIDS in Geneva reports that patients with wasting given 40 grams a day of glutamine (along with NAC, vitamins C and E, selenium and beta-carotene) gained an average of 1.7 kilograms (3.75 lbs) in lean body mass in 12 weeks. Patients in the control group were given glycine (another amino acid protein) and a multivitamin and they did not gain similarly.
Shabert notes that patients in a recent study using human growth hormone (which can have many unwanted side effects) put on a similar amount of weight in the same time period. But when they were followed up after stopping treatment, they lost the weight. Glutamine supplementation cost $250 while human growth hormone cost about $9,500. According to Shabert, growth hormone "may force the body to make muscle at the expense of other vital organs." She says that the death rate of people using growth hormone was slightly (not significantly) higher than for the controls.
In support of Smigelski's views on glutamine and lipodystrophy, none of Shabert's subjects on glutamine developed the problem even though almost all were on protease inhibitors. However, it was a small study with only 21 subjects and its end point was never intended to find lipodystrophy.
Dr. Mary Romeyn, a physician with a large HIV practice in San Francisco and author of the 1998 book, "Nutrition and HIV", says that low glutamine levels may be responsible for bad reactions to Bactrim -- so, those who need Bactrim might want to consider supplementation with glutamine.
Few physicians or nutritionists report any toxicities or side effects from glutamine even at high doses. Says Smigelski, "It may heighten the effects of caffeine" -- which, for many, might be a plus. People with liver disease need to count their glutamine dose as part of their protein allotment, and some believe that it can help liver health. However, people with end stage liver or renal disease may have trouble. According to Dr. Charles Noyer, who published a study of glutamine for intestinal problems in PWAS, people might have "changes in mental status", including lethargy and sometimes even mania. In his study, no one suffered these effects, however. Dr. Shabert reports that a study of glutamine in people awaiting liver transplant found that it caused encephalopathy (brain dysfunction), but she hasn't had any problems using it so far.
Smigelski recommends the following dosages, to be adjusted according to individual needs and responses. For diarrhea caused by protease inhibitors, IO grams a day. To treat symptoms of infectious diarrhea, use 30 grams a day for one week. As a treatment for the symptoms of diarrhea caused by MAC or cryptosporidiosis, use 40 grams a day for a week. Maintenance dosages should be adjusted according to individual needs. Shabert's study found 40 grams a day helped people with wasting add lean body mass. All experts agree that Glutamine works best in combination with other anti-oxidants. Smigelski believes that it's never too early to start supplementation. For people with HIV he recommends 5-10 grams a day of glutamine, 1-2 grams NAC, along with Vitamins C, E and selenium (we might add beta-carotene, garlic and thioctic acid).
Most nutritionists prefer the powdered form of glutamine. It should be dissolved in water or juice and consumed quickly before it breaks down. Capsules are available, but it's believed that the powder is better absorbed and the number of capsules needed to reach your dose might actually promote diarrhea or gas because of the gelatin coating. Glutamine should be taken immediately before or after meals. Doses should be spread out to three or more times a day.
What People on Glutamine are Saying?
John, a client of the PWA Health Group, believes he's been HIV-infected since 1978 -- he had persistent generalized lymphadenopathy (lymph node enlargement) before AIDS was discovered. "I've been through all the drugs," he says. "I have multidrug resistant HIV."
John takes the full range of anti-oxidant supplements including alpha lipoic acid, NAC, vitamin C and 8-10 grams a day of glutamine. He started on the regime because, "I thought that one factor that was not being considered in HIV was the host." He laughs, "I'm the hostess with the mostess," but he didn't want to provide a party atmosphere for his virus. John says that glutamine didn't help when he had diarrhea related to Viracept, but other than that, he hasn't had a problem with diarrhea. "I know other people who take it, (glutamine) who believe they have seen an effect." As for his current health, "I'm OK. I can't see cause and effect, but I have no other real options." His T-Cell count is 370 and he does report serious fatigue, but no side effects related to glutamine.
Mark, also a client of the PWA Health Group, had an unwanted change in his numbers just after starting glutamine, but has no way of knowing whether it was related to the supplement. "For a year, I watched my numbers fluctuate," he said. He started an anti-oxidant cocktail and, "My numbers got worse. My lowest T-Cell count went down to 209. 1 stopped everything. I got it in my head that the glutamine was the problem because I thought it was the most important of the anti-oxidants."
Mark, a "long term survivor", believes he became infected in the 70's, although unlike John, he has never met the definition for AIDS. Now, he says, "I'm healthy as a horse." He was taking all the anti-oxidants but glutamine and recently added it back into his regimen. His numbers are still fluctuating.