Future directions

Although glutamine is composed of merely 5 carbon atoms and 2 amino moieties, it has a multitude of important functions that have been elucidated through research over the past several decades. Glutamine is involved in diverse processes across different organ systems, including the gastrointestinal, central nervous, immune, and circulatory, to name a few. Wound healing is a complex series of events involving the different types of immune cells that cause inflammation, cell proliferation, and new tissue formation. Glutamine is important for all of these aspects, as it increases proliferation of inflammatory cells, enhances neutrophil phagocytic capability, and is involved in fibroblastic formation of collagen. However, more research needs to be done to clarify the direct effects of glutamine supplementation or deficiency on local wound healing. Clearly, glutamine is important to inflammatory cells metabol-ically, but whether a deficiency in glutamine causes delayed wound healing is unclear. Simple animal studies looking at wound tensile strength and wound histology over time in relation to glutamine levels would help answer this important question. Additionally, novel methods of glutamine delivery to wounded tissue could be developed that would eliminate the need for parenteral supplementation.

Other effects of glutamine, while lesser known and publicized, warrant further investigation. The relationship between glutamine and taurine, a potent osmoregu-lator during times of stress, needs further exploration. Taurine is reduced after surgery or during critical illness and may play an important role in the fluid shifts that are often seen in these states. How glutamine regulates taurine levels and how this can be manipulated for the benefit of the patient needs to be elucidated. Glutamine in the form of glutathione protects the body from oxidative stresses that can cause apoptosis, or programmed cell death. Ischemia/reperfusion injury is encountered in many disciplines of surgery. Revascularization of an extremity in vascular surgery, anastomosis of muscle flaps in plastic surgery, and transplantation of organs can all lead to ischemia/reperfusion injury. There are good basic science studies that have shown that glutamine has a definite function in increasing glutathione levels and decreasing oxidative stress. Application of this data in animal models of ischemia/reperfusion injury could help elucidate ways of increasing tissue flap and organ transplant viability.

There have been many clinical trials examining the supplementation of glutamine parenterally and enterally in the postsurgical as well as critically ill patient. The statistical quality and power of these clinical trials vary, as do their results. In some studies, supplemental glutamine was shown to be beneficial, while in others, it was not. Larger clinical studies that are adequately powered to show statistical significance are warranted. The exact amount and length of glutamine supplementation needed to achieve a benefit is not known. Dosing levels at which toxicity or adverse side effects occur are also not known. Research into dosing, bioavailability, and new methods of delivery could prove helpful in the future, as more basic science and clinical research on this most versatile amino acid comes to fruition.

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