This article [Kawaguchi et al., 2005: (http://ajpregu.physiology.org/cgi/reprint/288/6/R1612)(http://www.ncbi.nlm.nih.gov/pubmed/15705802?dopt=Abstract)] shows that exogenous glutamine, without concomitant hyperammonemia (abnormal elevation of ammonia) can inhibit the dilation of cerebral arterioles (the smaller-diameter branches of the pial arteries that run along the outer surface of the brain) in rats, and exogenous arginine can block the effect, to some extent. There are lots of articles that show the same thing, and, in my opinion, this shows that elevating the plasma glutamine levels would only be expected to be beneficial up to a point. There's quite a bit of evidence, discussed by Kawaguchi et al. (2005), that the effect of glutamine is the result of its competition with citrulline for transport into endothelial cells or perivascular nerve fibers (fibers that induce nitric-oxide-dependent vasodilation). Citrulline is converted into arginine, and arginine is then used as a substrate for nitric oxide biosynthesis by eNOS. The citrulline formed as a product is then recycled, and an excess of glutamine is thought to inhibit the recycling (or the transport of citrulline into cells from the blood) of citrulline. The authors also noted that glucosamine, formed from glutamine, could have produced the impairment in vasodilation. I think only a small percentage, about 3 percent, of glutamine is converted into glucosamine in the liver, but I don't know what percentage is converted into glucosamine in endothelial cells or neurons (i.e. perivascular neurons, etc.).
Although a person could, in my opinion, conceivably help to minimize this type of effect by taking glutamine with meals (thereby preventing spikes in plasma glutamine and deliberately limiting its bioavailability) and spreading the dosages out across the day, it's important to consider the drastic reductions in plasma glutamine that can occur, for example, during and after intense exercise or in catabolic disease states. Keast et al. (1995) [Keast et al., 1995: (http://www.ncbi.nlm.nih.gov/pubmed/7845291)] found that high-intensity exercise depleted plasma glutamine levels by more than half, and more than 6 days were required for the restoration of pre-"overtraining" plasma glutamine to occur in some of the athletes. For some reason, there's been an obsessive focus on controversy about the role of glutamine depletion in the immunosuppressive effects that high-intensity exercise can have. I don't know why there has been so much focus on that aspect of glutamine metabolism, but it doesn't matter if glutamine depletion is not a major role in exercise-induced immunosuppression. By definition, someone who can exercise at high intensities is going to be fairly "healthy," and this makes the entire debate, surrounding that specific issue, seem bizarre to me. For example, Walsh et al. (1998) [Walsh et al., 1998: (http://www.ncbi.nlm.nih.gov/pubmed/9562294)] found not-very-drastic reductions in plasma glutamine following exercise (of poorly-defined intensity) but took the measurements in "well-trained" athletes. In my mind, the capacity of an athlete to replenish glutamine levels in his or her blood or muscles or heart or endothelial cells is going to be fairly robust. A major point of the hundreds of articles showing immunostimulatory effects of glutamine in trauma patients, etc., is that one cannot, in my opinion, look at the results of studies in elite athletes and then generalize or apply those results to a discussion or analysis of glutamine or cell-energy metabolism in the context of disease states.
That's unrelated to the original topic, and it's still important, in my opinion, to take seriously the possibility of a nitric-oxide-suppressive effect of excessively-high glutamine intakes, particularly in the absence of arginine. It's worth noting that significant portion of glutamine is converted into citrulline and alanine in the intestinal tract, and the blood-borne citrulline can then be converted into arginine in the kidneys or, locally, in endothelial cells. So that would tend to oppose or counteract the supposed vasoconstrictive effects of abnormal elevations in plasma glutamine. But the idea, in my opinion, is not really to induce supraphysiological levels of plasma glutamine. Other approaches, besides limiting the dosage of glutamine and taking the glutamine in smaller dosages with meals, would be to use arginine simultaneously, as I've discussed in past postings. The first article I linked to (together with other articles) suggest to me that the ratio of arginine to glutamine, in approaches to supplementation, would be an important factor in limiting some of these effects. But, for this and other reasons, in my opinion, the dosage of glutamine at which this type of effect might occur would be different for every person and would depend on his or her activity level. It's always good for a person to talk to his or her doctor about this type of issue. As with anything, there tends to be a therapeutic dosage range and a range at which side effects begin to occur. It's interesting that Spolarics et al. (1991) [Spolarics et al., 1991: (http://www.ncbi.nlm.nih.gov/pubmed/1872392)] found evidence that glutamine, along with fatty acids, is a major energy source for endothelial cells in blood vessels perfusing the liver. Free fatty acids (FFAs), similarly, can be major energy sources for cells in some tissues, under some circumstances, but also can inhibit mitochondrial functioning and interfere with insulin sensitivity and cause other problems, etc. The roles of glutamine in cellular energy metabolism aren't as murky as the roles of FFAs are, but the point is that physiological substrates and compounds tend to not simply be either "good" or "bad."
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