Concepts and Controversies in Nutrition

Jacqueline Jones Wessel, MEd, RD


March 11, 2002

In This Article

Immune-Enhancing Formulas

Immune-enhancing formulas (IEFs), also known as immune-modulating formulas, include arginine, glutamine, nucleic acids, and omega-3 fatty acids. The concept behind these formulas is to protect and stimulate the immune system with the goal of reducing infectious complications, decreasing multiorgan failure, decreasing time on mechanical ventilation, and decreasing length of hospital or intensive-care stay.

Dr. Daren Heyland[1] from the Department of Medicine, Queen's University, Kingston, Ontario, Canada, discussed the possibility that the use of IEFs in the critically ill may inflict harm. Dr. Heyland performed a meta-analysis of 326 citations; 22 of 60 human randomized studies met eligibility requirements for inclusion in the analysis. Clinical studies that compared IEFs with total parenteral nutrition (TPN) or oral diets or intravenous (IV) fluids were excluded. A total of 2419 patients were included in the 22 randomized trials, including critically ill patients, burn patients, trauma patients, and patients undergoing major elective surgery. Overall, Dr. Heyland concluded that the use of IEFs may decrease infectious complication rates. The treatment effect depended on the patient population, the intervention, and the methodologic quality of the study. The subgroup of elective surgical patients is different from other critically ill patients; elective surgical patients have decreased rates of complications. Immunonutrition is associated with a reduction in infectious complications without any effect on mortality. In critically ill patients, immunonutrition is not associated with any apparent clinical benefits and may be harmful. Dr. Heyland's overall conclusion was that immunonutrition could not be uniformly recommended for all critically ill patients.

Commercially available IEFs vary and contain different immune-enhancing nutrients. Arginine is the most common immune-enhancing ingredient contained in the different formulas; the amount of arginine contained in each formula differs. Substitution of one formula for another cannot be done, and the optimal amount of the immune-enhancing ingredients is not known. The formulas have other ingredients that may affect outcome as well as other variables of calories and nitrogen intake as related to estimated need.

In lieu of a definitive conclusion on the best use of IEFs, the IEF summit group suggests that the following patient groups are best suited to receive IEFs:


  • Moderately malnourished patients undergoing upper gastrointestinal surgery

  • Severely malnourished patients undergoing lower gastrointestinal surgery

  • Trauma patients with an injury severity score of 18 or greater

  • Trauma patients with an Abdominal Trauma Index of 20 or more


Other patients may benefit from IEFs but the degree of benefit is less clear than for patients previously described. Patients undergoing elective surgery such as aortic reconstruction with known chronic obstructive pulmonary disease, patients with head and neck surgery and preexisting malnutrition, patients with severe head injury, patients with a Glasgow Coma Scale score of less than 8, patients with ≥ 30% third-degree burns, and ventilator-dependent, nonseptic medical and surgical patients are examples of patients for whom therapy with an IEF may be beneficial.

Patients who are not thought to be good candidates for IEFs include those expected to be eating ad lib within 5 days, those in the ICU for monitoring only, those with a bowel obstruction distal to the enteral access site, those with incomplete resuscitation, and those with a major upper GI hemorrhage.

IEFs should be initiated before the insult whenever possible. In the case of elective surgery, IEF feeding should be started 5-7 days prior to surgery. If preoperative nutrition cannot be started and gastroparesis is expected, insertion of jejunal access would be advised and feedings started as soon as it is clinically safe.

The rate of advancement is somewhat dependent on tolerance; however, the diet should be advanced until at least 1200-1500 cc is given daily or until at least 50% to 60% of the calculated enteral goal is met. The threshold amount necessary for clinical effect is not yet known.

No specific data regarding the optimal length of time for IEF is available.

Despite 60 randomized human studies, clinical studies of IEFs have yet to identify their optimal effect and role in therapy. More clinical research is needed before more precise guidelines can be recommended.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: