Glutamine Metabolism and Transport in Skeletal Muscle and Heart and Their Clinical Relevance
Michael J Rennie, Aamir Ahmed, Shihab E. O. Khogali, Sylvia Y. Low, Harinder S. Hundal and Peter M. Taylor
Department of Anatomy and Physiology, University of Dundee, Dundee, DD1 4HN, Scotland, United Kingdom
The following in an excerpt from the paper illustrating the authors' opinion of the clinical benefits of glutamine. The entire paper can be viewed in PDF format here.
Important questions regarding the clinical use of glutamine
The evidence that glutamine has beneficial effects in certain circumstances is, I believe, now substantial. Nevertheless, it seems unlikely that the major beneficial clinical effects of glutamine are due to effects in skeletal muscle (although there may be some more direct beneficial effects in heart). We know that the major requirements for the glutamine produced by skeletal muscle are to subserve functions of acid-base balance, the provision of fuel for small intestinal enterocytes and provision of fuel and nucleic acid precursors for cells of the immune system. Thus, provision of exogenous glutamine may simply spare skeletal muscle from the task of producing increased amounts of glutamine. The anabolic effects of glutamine on skeletal muscle may help preserve muscle mass, which will be important in the long-term rehabilitation of patients after severe injury or disease but is unlikely to be important in tipping the balance between life or death. However,the possibility that glutamine may stimulate glycogen resynthesis may be important for the maintenance of muscle function and possibly even for weaning patients from ventilators because it is likely that ventilatory muscle fatigue is associated with low availability of intramuscular glycogen.
Nevertheless, the ability to control acid-base balance, to maintain the structural integrity and barrier functions of the gut and to maintain and enhance immune function are likely to be much more important in critically ill patients.Unfortunately, we are rather short of hard data derived from studies in patients (rather than animals) concerning the beneficial effects of glutamine supplementation on acid-base balance, structural integrity of the gut and immune function. There is, as far as I know, as yet no good evidence that provision of exogenous glutamine helps a sick patient to dispose of a proton load more efficiently. Furthermore, although exogenous glutamine can enhance transport functions of the small intestine (Tremel et al. 1994, Van der Hülstet al. 1993) in postoperative patients and provision of exogenous glutamine intraoperatively leads to a greater glutamine uptake by small intestinal tissues (Soeters, P. B., personal communication), there is no evidence from clinical studies in humans that the intestinal barrier function against bacteria is enhanced. There may be evidence in animals that this is the case (Deitch 1994) and that structural features of the small intestine such as villus height or mitotic index are preserved, but crucial evidence concerning human pathophysiology is not yet available. Also, although there is no doubt that immune cells require glutamine as an oxidative fuel and to support cell division (Newsholme et al. 1988), it is difficult to find good clinical studies in which provision of glutamine has been associated with an improvement in immune status or, more to the point, immune function.
What about dose response? It appears that amounts of glutamine up to 20 g/d may be required in patients with moderate to severe injury (Stehle et al. 1989), and amounts up to 40 g/d have been given safely in patients undergoing bone marrow transplant (Ziegler et al.1994). However, there are no good dose-response data currently available.
Does the route of delivery matter? If the aim is to replenish skeletal muscle, then it may be better to give glutamine intravenously, but so long as the needs of the splanchnic bed can be met relatively modestly, say by up to 6 g of glutamine per day, then enteral provision should also allow replenishment of peripheral glutamine stocks. However, the capacity of the gut for glutaminolysis is large and possibly inducible, so provision of enteral glutamine may not be the best way of feeding the periphery if enterally provided glutamine is simply catabolized.