Glutamine and wound healing

Advances in Skin & Wound Care, Sep/Oct 2002 by Collins, Nancy

Nutrition Q&A

Q: Should patients with wounds be supplemented with glutamine? If so, how much should be given each day and in what form?

A: L-glutamine is a nonessential amino acid, meaning that glutamine can be readily synthesized by the human body via activity of the enzyme glutamine synthetase. L-glutamine is the most prevalent amino acid in the bloodstream, accounting for 30% to 35% of the amino acid nitrogen in plasma.1 It has long been thought that glutamine was not a necessary component of the oral diet because of the relative amount of glutamine in the body compared with other amino acids and the fact that the body can independently produce glutamine.

Generally, an average diet contains 5 to 10 grams of glutamine per day. In healthy people, dietary intake and synthesis of glutamine is balanced with demand.1 The idea of supplementing glutamine arose from the belief that during times of stress or injury, the metabolic demand for glutamine can exceed the capacity of skeletal muscle to release it.2 For this reason, glutamine is often labeled as a conditionally essential amino acid. Functions of Glutamine

Glutamine is the primary nutrient and energy source for the cells that line the intestinal tract and for the immune system. Enterocytes, colonocytes, lymphocytes, and fibroblasts use glutamine as a primary fuel.3 It is also essential for DNA synthesis and cell growth, and it functions as an important antioxidant that may be protective in a variety of circumstances.4 Glutamine plays a central role in various aspects of metabolism, including the synthesis of glutathione and nucleic acids, nitrogen transport between organs, and muscle maintenance.5

Role of Glutamine in Stress A patient with a wound, particularly a nonhealing wound, may be in a catabolic state from the classic stress response involving increased levels of catecholamines and cortisol. The catabolic state is characterized by breakdown of lean body mass that results in a negative nitrogen balance and muscle wasting.6 Patients with wounds may also be hypermetabolic; their nutritional needs are elevated because of the increased workload caused by the wound. During these periods of metabolic stress, the muscle produces significantly more glutamine to maintain blood levels.Yet intracellular glutamine concentrations may fall by at least 50%,3 suggesting that glutamine supplementation is needed.

Differing Opinions

Not all researchers agree with this assumption, however. Some question whether this deficiency actually occurs and, if so, whether it is clinically significant.

Buchman7 believes that decreased blood concentrations of glutamine do not necessarily indicate a deficiency state. According to his research, intracellular glutamine concentrations generally decrease in catabolic, critically ill patients; the increase in subsequent endogenous synthesis cannot completely offset the loss. However, he concludes that the clinical significance of this finding has not been shown. The abstract of his review article states, "On the basis of currently available clinical data, it is inappropriate to recommend glutamine for therapeutic use in any condition."

On the other hand, Demling and DeSanti8 conclude that the anticatabolic effects of increased administration of glutamine appear valid for all injured patients. They state that they routinely administer glutamine to the bum patients they treat.

Interest in glutamine has increased during the past decade. However, many of the studies have been conducted with patients receiving parenteral nutrition, which may present a different scenario than with patients fed enterally.

Supplementation Recommendations

The optimal amount and form of oral glutamine required to achieve beneficial results is unknown. Some sources say that the addition of 20 to 40 grams of glutamine per day is safe and well tolerated in adults.2 Another recommendation is to base dosage on 0.5 gram of glutamine per kilogram of actual body weight.3 For example, a 110-pound (50-kg) patient would receive 25 grams of glutamine daily Either way, it is best to give glutamine in divided doses throughout the day.

A variety of glutamine products are available. Nutraceuticals, owned by Baxter Healthcare Corporation, Deerfield, IL, makes several glutamine products, including Restore-X, a single dose packet of powder that is mixed with a patient's beverage of choice. It may also be used in tube feedings. Each packet contains 10 grams of glutamine and 75 kcal, plus 20 mg of zinc, 500 mg of vitamin C, 5000 IU of vitamin A, 140 mg of arginine, and other vitamins.9

In addition, Novartis Nutrition, Minneapolis, MN, recently introduced a product called GlutaSolve, a powdered product that is mixed with hot or cold beverages. Each 22.5-gram packet contains 15 grams of glutamine and 90 kcal.10 It is lactose-free, sugarfree, gluten-free, and cholesterol-free, and it may be used with tube feedings.

Glutamine supplements should be used with caution in patients with hyperammonemia, hepatic failure, or renal failure because it may lead to excess ammonia production in these patients.2