Summary:Painful oral mucositis is a common complication after bone marrow transplantation (BMT). Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium. This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT. Glutamine or a placebo (glycine) were administered from admission until day +28 in 193 BMT patients in a randomized, double-blind, placebo-controlled study at a dose of 1.0 g amino acid/m 2 /dose swish and swallow four times a day. In autologous BMT patients (n = 87) glutamine was associated with significantly less mouth pain by self report and by opiate use (5.0 ؎ 6.2 days of morphine for glutamine vs 10.3 ؎ 9.8 days for placebo; P = 0.005). Matched sibling BMT patients had no effect by self report and an increased duration of opiate use (23.2 ؎ 5.7 days for glutamine vs 16.3 ؎ 8.3 days for placebo) (P = 0.002). However, day 28 survival of allogeneic patients was improved by glutamine. No significant differences in TPN use, rate of relapse or progression of malignancy, parenteral antibiotic use, acute or chronic GVHD, or days of hospitalization were observed in either autologous or allogeneic recipients. No toxicity of glutamine was observed. We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients, possibly due to interaction with methotrexate. Keywords: mucositis; stomatitis; supportive care; nutrition; epithelium; chemotherapy Many of the major adverse effects of BMT are related to disruption of mucosal integrity from high-dose chemotherapy and/or radiation-induced damage of oral and intestinal epithelium. Preclinical studies have demonstrated less damage to rat intestinal epithelium if high doses of enteral glutamine were included in the diet during and after 1000 cGy of whole abdominal radiation. [1][2][3] Glutamine is the most abundant amino acid in the blood, but is generally absent Correspondence: Dr P Anderson, Pediatrics-East 9, Mayo Clinic, Rochester, MN 55905, USA Received 7 November 1997; accepted 16 March 1998 from total parenteral nutrition (TPN) for solubility and stability reasons. [4][5][6][7] The intestine utilizes glutamine as its primary energy source, and glutamine has been shown to be an essential dietary component for support and maintenance of intestinal growth and function. 8-10 Supplementation of TPN with glutamine has been shown to decrease villous atrophy associated with exclusive feeding via TPN. 11,12 Nutritionally depleted patients have been shown to have decreased plasma glutamine and mucosal glutamine. 13 Recent studies have also demonstrated a survival advantage of TPN supplementation with glutamine in critically ill patients. 14 Since no information was available concerning the effect of oral glutamine on the squamous epithelium of the oropharynx after chemotherapy and/or radiation, we conducted an earlier pilot study using oral glutamine 4 g/m 2 t...