Department of Dietetics, the Nutrition Support Team, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

BACKGROUND: Malnourished head and neck cancer patients are at increased risk of postoperative complications.

OBJECTIVE: We studied the effect of perioperative, arginine-supplemented nutritional support on nutritional status, immune status, postoperative outcome, and survival in severely malnourished (weight loss >10% of body weight) head and neck cancer patients undergoing major surgery.

DESIGN: Forty-nine patients were randomly assigned to receive 1) no preoperative and standard postoperative tube feeding, 2) standard preoperative and postoperative tube feeding, or 3) arginine-supplemented preoperative and postoperative tube feeding.

RESULTS: Patients in both prefed groups received approximately 9 d of preoperative tube feeding, resulting in energy intakes of 110% and 113% of calculated needs (compared with 79% in the control group; P = 0.007). Compared with no preoperative feeding, preoperative enteral nutrition did not significantly improve nutritional status or any of the studied biochemical or immunologic indexes. Major postoperative complications occurred in 53%, 47%, and 59% of patients in study groups 1, 2, and 3 (NS). A trend was seen toward better survival in the arginine-supplemented group (P = 0.15). Secondary analysis showed that survivors had better human leukocyte antigen-DR expression on monocytes (P = 0.05) and higher endotoxin-induced cytokine production (P = 0.010 for tumor necrosis factor alpha and P = 0.042 for interleukin 6) at the start of the study than did patients who died.

CONCLUSIONS: Nine days of preoperative tube feeding, with or without arginine, did not significantly improve nutritional status, reduce the surgery-induced immune suppression, or affect clinical outcome in severely malnourished head and neck cancer patients. Patients supplemented with arginine-enriched nutrition tended to live longer. Some markers of immune function may distinguish patients with good or bad prognoses.

PMID: 11157331 [PubMed - indexed for MEDLINE]

Glutamine is an important precursor for de novo synthesis of arginine in humans.

Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.

BACKGROUND: A metabolic relation exists between glutamine and arginine, 2 amino acids with properties that enhance the recovery of seriously ill patients. It is possible that glutamine exerts part of its beneficial effects by enhancing the availability of arginine.

OBJECTIVES: We aimed to quantify under postabsorptive conditions the metabolic pathway of plasma glutamine into arginine via the intermediate citrulline and to establish the contribution of the kidneys to the synthesis of arginine.

DESIGN: The study was conducted in patients during surgery. The metabolism of glutamine, citrulline, and arginine was studied by using intravenous administration of stable isotope tracers of the amino acids. Results were interpreted by using established equations. Parametric tests were used to test and correlate results. P < 0.05 was regarded as significant.

RESULTS: Mean (+/-SE) whole-body plasma turnover rates of glutamine, citrulline, and arginine were 240 +/- 14, 6.2 +/- 0.6, and 42 +/- 2.9 micromol x kg(-1) x h(-1), respectively (P < 0.01). Plasma turnover of citrulline derived from glutamine was shown to be 5.1 +/- 0.7 micromol x kg(-1) x h(-1), and arginine derived from citrulline was shown to be 4.9 +/- 0.9 micromol x kg(-1) x h(-1) (P < 0.01). The contribution of plasma glutamine to plasma arginine derived from plasma citrulline was calculated to be 64%. The kidneys were observed to take up >50% of circulating plasma citrulline and to release equimolar amounts of arginine into plasma.

CONCLUSIONS: This study shows that glutamine is an important precursor for the synthesis of arginine in humans. It also provides a firm basis for future studies exploring the effect of a treatment dose and the route of administration (enteral or parenteral) of glutamine.

PMID: 18469251 [PubMed - indexed for MEDLINE]

1: Crit Care Med. 2007 Sep;35(9 Suppl):S568-76. Links

Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator?

Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.

OBJECTIVE: Glutamine and arginine are both used as nutritional supplements in critically ill patients. Although glutamine has been shown to be beneficial for the metabolically stressed patient, considerations about arginine supplementation are not unanimously determined. Our aim is to review the current knowledge on the possible interplay between glutamine and arginine generation in the stressed patient and to elaborate on whether these amino acids may function as a common denominator. Because glutamine can be given by the parenteral and enteral routes, possible different actions on the metabolic fate (e.g., generation of citrulline) with both routes are analyzed. DATA

SOURCE: A summary of data on the clinical effect of glutamine and arginine metabolism is given, incorporating data on glutamine and arginine supplementation. Differences between the route of administration, parenteral or enteral, and the molecular form of supplied glutamine, free or as dipeptide, on citrulline generation by the gut and production of arginine are discussed.

RESULTS: Glutamine and arginine influence similar organ systems; however, they differ in their targets. For example, glutamine serves as fuel for the immune cells, increases human leukocyte antigen-DR expression on monocytes, enhances neutrophil phagocytosis, and increases heat shock protein expression. Arginine affects the immune system by stimulating direct or indirect proliferation of immune cells. This indirect effect is possibly mediated by nitric oxide, which also enhances macrophage cytotoxicity. Furthermore, glutamine serves as a precursor for the de novo production of arginine through the citrulline-arginine pathway. Glutamine has shown to be beneficial in the surgical and critically ill patient, whereas arginine supplementation is still under debate. The route of glutamine administration (parenteral or enteral) determines the effect on citrulline and on the de novo arginine generation. There is a marked difference between the administration of free glutamine and dipeptide enterally or parenterally. Splanchnic extraction of the hydrolyzed glutamine in mice when administering the dipeptide enterally is higher compared with administering free glutamine from the enteral site. In patients, splanchnic extraction of the dipeptide given enterally is 100% when comparing supplementation of the dipeptide intravenously.

CONCLUSIONS: The beneficial effects of free glutamine or dipeptide may depend on the route of administration but also on the metabolic fate of amino acids generated (e.g., citrulline, arginine). Glutamine serves as a substrate for de novo citrulline and arginine synthesis. More research needs to be done to establish the direct clinical relevance of the different metabolic pathways. Future perspectives might include combining enteral and parenteral routes of administrating free glutamine or dipeptide.

PMID: 17713411 [PubMed - indexed for MEDLINE]

1: Nutr Hosp. 2008 Mar-Apr;23(2):105-10. Links

Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial.

Department of Otorhinolaryngology, La Paz University Hospital, Madrid, Spain. pablocasas@clinicasas.es

INTRODUCTION: Significant malnutrition exists in a high percentage of patients with head and neck cancer. Malnutrition is associated with defects in immune function that may impair the host response to malignancy. Malnutrition and immunosupression make patients highly susceptible to postoperative infections and complications.

OBJECTIVES: Compare two immunoenhanced enteral nutritions with a control diet, and evaluate the effect in postoperative infections, length of stay and inflammatory markers.

PATIENTS: A population of 44 patients with oral and laryngeal cancer was enrolled in a randomized trial. At surgery, patients were randomly allocated to three groups: (group I); patients receiving an arginine-enhanced formula (group II); patients receiving a standard polymeric formula, and (group III) patients receiving an arginine, RNA and omega-3 fatty acids enhanced formula, in an isonitrogenous way.

RESULTS: The duration of enteral nutrition in the three groups was similar with an average duration of 14,5 +/- 8 days. The length of postoperative stay was similar, with an average of 19,8 +/- 8,5 days. Wound infections and general infections were more frequent in the control group. Fistula rates were not improved in the enhanced diet groups. No significant intergroup differences in the trend of the two plasma proteins (albumin, transferrin), lymphocytes, weight, IL-6, CPR and TNFalpha were detected. The control group showed the highest levels of TNFalpha at the fourteenth postoperative day. Gastrointestinal tolerance and diarrhoea rate were similar in all the patients.

CONCLUSIONS: Immunoenhanced enteral nutrition formulas improved the infection rate in the postoperative of head and neck cancer patients. In the fistula rates, we observed that technical problems and nutritional status might have played an equally important role, and therefore the positive effect of immunonutrition in this parameter might have been overestimated.

PMID: 18449445 [PubMed - in process