Thursday, June 7, 2012

Glutamine and the brain by Jerry Brainum

A few years ago, glutamine went from being an obscure, conditionally essential amino acid to the latest nutrient "star." This elevated status was based on findings that glutamine seemed to help preserve muscle under highly stressful conditions that featured a major loss of body protein. Such conditions included severe burns, after major surgical procedures, and any catabolic illness characterized by major protein loss. This isn't a trifling issue, either, since it's the loss of protein that spells impending death for patients suffering from such catabolic illness as AIDS and cancer. Glutamine was used in parenteral nutrition formulas to help stabilize hospitalized  catabolic patients. One physician who was involved in providing nutrition for such patients, Scott Connelly, realized that glutamine could be of value to athletes and bodybuilders, and glutamine became the "secret" ingredient in his Met-rx food supplement.
     It made sense that glutamine supplementation would be of value to athletes, since glutamine is the most abundant amino acid in muscle and blood, comprising 60% of the amino acid content of muscle. Glutamine plays a role in the body's synthesis of urea, the major nitrogen waste product of protein metabolism. It's also vital for helping the body to degrade ammonia. Glutamine also acts as a nutrient precursor for glutathione, one of the most important built-in antioxidants in the body.Glutamine is called a "conditionally essential" amino acid because normally the body can produce glutamine from other amino acids, such as glutamic acid. But under high stress conditions, the body is unable to keep up with the metabolic demand demand for glutamine, and it then becomes essential for health. Among other functions, glutamine is required for activation of certain immune cells, as well as use as an energy source for producing new cells in the intestinal tract.Glutamine protects cells against stress effects by activating special cellular protection proteins called heat shock proteins.These heat shock proteins temper the activity of inflammatory factors produced under stress. Out of control inflammation has a catabolic effect in muscle. Indeed, some studies show that glutamine is capable of blunting the effects of cortisol, the major catabolic hormone in the body, as well as myostatin, a protein that blocks muscle growth.
   The most controversial aspect of glutamine is its role in protein synthesis and muscle growth. While the putative mechanisms of glutamine, such as interference with both cortisol and myostatin, should favor an anabolic milieu in muscle, studies where supplemental glutamine have been provided to bodybuilders have shown little or no effect on muscle protein synthesis and muscle growth. On the other hand, a key cellular anabolic signaling factor in muscle cells is their state of hydration. A hydrated cell is anabolic, while a dehydrated cell is catabolic. Glutamine provides potent effects in promoting cellular hydration. In the cell, glutamine promotes a potent osmotic effect, pulling water into the cell, which boosts cell hydration.Glutamine may also help increase muscle and liver glycogen stores depleted after exercise. Studies show that those who follow the popular low-carb diet plans have 25% lower stores of glutamine.Some studies suggest that glutamine may promote the release of growth hormone, as well as gonadotropin-releasing hormone, which would have the effect of boosting testosterone release in the body. With its favorable effects on anabolic hormones, coupled with its blunting of catabolic factors, such as cortisol and myostatin, it's hard to understand how glutamine would not be of use to bodybuilders. Indeed, studies show that glutamine can offset the blunting of immune response that is common after intense exercise.
    A recent study illustrated an interesting role of glutamine in the body.The study noted that the brain contains high levels of glutamine synthetase, the enzyme that produces glutamine in the body.Apparently, this high level of the glutamine-producing enzyme offers potent brain protection through various means.GS is particularly active in the frontal lobe of the brain, the site of memory and intelligence, and the site most prone to neurodegenerative disease. In diseases of the brain, GS activity is blunted, which means there is less glutamine produced in the brain.A major cause of the damage induced by such diseases as Alzheimer's disease is excess inflammation. Much of this inflammation results from the activity of oxidants. Glutamine acts as an antioxidant in the brain, and also blocks the activity of inflammatory substances that kill brain cells.Not only that, but glutamine can help repair DNA damage in the brain, preventing excess brain damage.In the body, 800 DNA lesions occur per hour in cells, about 19,200 hits a day.DNA repair normally takes care of this, but the DNA repair mechanisms tend to downgrade with age. In some people, however, DNA repair is maintained, and those are the folks who live to 100 or more. A process called autophagy allows the body to degrade and remove old cells that aren't working or are damaged. This process is necessary for the body to replace those cells with new cells. When glutamine levels are reduced in the brain, autophagy slows, allowing the build-up of damaged cells that can result in brain degeneration. So it seems that glutamine is required for protecting the brain against stress, and in this manner, can also protect against the onset of diseases such as Alzheimer's.
    But what about those studies showing that glutamine seems to be useless for building muscle? For one, glutamine works best under catabolic conditions, and unless you are training extremely intensely, to the point of overtraining, the normal stores of glutamine in the body will indeed be enough to cover your needs, and taking supplemental glutamine won't add much. But the situation changes dramatically when you either overtrain, or train especially hard. In that case, the body will be unable meet the increased demand for glutamine, and some supplemental glutamine would likely be of some benefit.
    The main problem with glutamine supplementation is that since it's used as a primary fuel by intestinal cells, most of the oral glutamine ingested is taken up by these cells, rather then delivered to the blood. One way around this is to consume small doses of glutamine, no more than 5 grams at a time, several times a day. A recent study found that a supplemental form of glutamine called Sustamine, which consists of a dipeptide form of glutamine (two bonded amino acids, in this case, glutamine and alanine) increased blood glutamine levels 224% above that of free form L-glutamine. This bonded form is the same type provided to catabolic hospital patients, since it's more stable in liquid solutions compared to free glutamine.

Chen, J, et al. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid, and H202-induced stress.Plus one 2012;7;e33177.

©,2012, Jerry Brainum.Any reprinting in any type of media, including electronic and foreign is expressly prohibited.