Home

Cancer Treatment Side Effects & Supportive and Palliative Care

L-Glutamine for mucositis

L- glutamine is an essential amino acid involved in cellular repair, therefore it appears that L-Glutamine may limit damage by reducing treatment-induced metabolic deficiencies and promoting healing of the mucose membrane.

Previous studies of L-glutamine to prevent oral mucositis have involved an oral preparation called AES-14. AES 14 is combined with a vehicle (Saforisª), which enhances its availability to cells of the mucous membrane. This oral combination has been shown to favorably affect the course of chemotherapy-induced mucositis.

A study of 29 patients with head and neck cancer receiving chemo-radiotherapy randomly assigned patients to receive daily intravenous L-glutamine or placebo. The control group had a 67% incidence of severe oral mucositis compared to 14% in the L-glutamine group, which also reported less pain. A feeding tube was required in 60% of patients in the control group, as compared to 14% in the L-glutamine group. No adverse side effects of L-glutamine were reported.

Positive results in reducing the severity and duration of oral mucositis have also been reported from a large randomized, double-blind, placebo-controlled, crossover, multi-center trial to determine the efficacy of AES-14 delivered in the proprietary base, Saforis ™. In this study, 326 breast cancer patients received an anthracycline-based regimen along with AES-14 or placebo over two subsequent crossover cycles. AES-14 reduced the incidence of clinically significant oral mucositis by 22% compared to the placebo group, while maintaining an excellent safety profile that was comparable to placebo. Patients receiving Saforis in Treatment Cycle 1 had a 36% lower incidence of oral mucositis when crossed over to placebo in Treatment Cycle 2, indicating a significant carryover effect (P = .027).

Another study examined the protective effects of a parenteral glutamine supplementation in patients with metastatic colorectal carcinoma receiving 5-fluorouracil (5-FU)/calcium-folinate (CF) chemotherapy. A total of 24 patients underwent three courses of 5-FU/CF chemotherapy and were randomized to receive parenteral glycyl-L-glutamine or placebo. Effects on gastrointestinal mucosa were assessed by endoscopic examinations and histomorphometric measurements. In the intervention group, a significant reduction in mucositis and ulcerations of the gastric (P < 0.01) and duodenal mucosa (P < 0.05) was documented after the third course of chemotherapy. In the same group, the villus height/crypt depth ratio was significantly higher after therapy than in the unsupplemented group (1st course P < 0.01; 3rd course P < 0.05). However, there were no significant differences in the incidence and severity of clinical side-effects.

A small trial involving 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. The duration of objective oral mucositis was shorter in the glutamine arm and the grade of objective oral mucositis was less severe in the glutamine arm. However, Glutamine did not reduce the duration of subjective oral mucositis except in those developing Grade 3 mucositis.

However, the evidence for the use of l-glutamine in bone marrow transplant patients is not as clear. A couple of studies using parenteral or oral glutamine in adult autologous transplant patients suggested that glutamine was not effective in decreasing oral mucositis.

Another pediatric trial in hematopoietic stem cell transplant (HSCT) recipients tested the effect of L-Glutamine in reducing mucositis in 120 children receiving chemotherapy. Patients were randomized in a double-blind manner to receive glutamine or glycine at a dose of 2 g/m(2)/dose (maximum dose 4 g) twice daily until 28 days post transplant or discharge if sooner. Mucositis was graded by use of a modified Walsh scale. The glutamine group demonstrated a reduction in mean number of days of intravenous narcotics use and total parenteral nutrition. There was no statistically significant difference in toxicity between the two groups. The authors concluded that Glutamine appears to be safe and beneficial in reducing the severity of mucositis and strongly recommend giving consideration to include oral glutamine supplementation as a routine part of supportive care of SCT patients.

Safety

L-glutamine has been shown to be safe at oral doses of 10 g daily in oncology patients.

Although no specific dosing studies have been reported, most clinical research has used between 250 mg and 1 g of the powdered root in capsules, taken one to four times daily.

Recommendation

Because of high reported safety and evidence reported by RCTs, l- glutamine seems a viable therapy for the prevention of oral mucositis in patients with head, neck and gastrointestinal malignancies undergoing chemotherapy and/or radiation treatment. There is some indication that l-glutamine therapy may also be useful for the prevention of oral mucositis in patients with other type of malignancies (such as blood related cancers) but data published until now have offered mixed results.

Show/Hide References

References - Hide References

  • Aquino VM, Harvey AR, Garvin JH, Godder KT, Nieder ML, Adams RH, Jackson GB, Sandler ES. A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. 2005 Oct;36(7):611-6.
  • Cerchietti LCA, Navignate AH, Lutteral MA, et al. Double-blinded, placebo-controlled trial on intravenous L-alanyl-Lglutamine in the incidence of oral mucositis following chemotherapy in patients with head and neck cancer. International Journal of Radiation Oncology Biology Physics. 2006;65:1330-1337.
  • Coghlin Dickson TM, Wong RM, offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE. Effect of oral glutamine supplementation during bone marrow transplantation. JPEN J Parenter Enteral Nutr. 2000 Mar-Apr;24(2):61-6.
  • Decker-Baumann C, Buhl K, FrohmŸller S, von Herbay A, Dueck M, Schlag PM. Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Eur J Cancer. 1999 Feb;35(2):202-7.
  • Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY. Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys. 2000 Feb 1;46(3):535-9.
  • Peterson DE, Jones JB, Petit RG 2nd. Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer. 2007 Jan 15;109(2):322-31.
  • Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, Kozak T. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Bone Marrow Transplant. 2002 Dec;30(12):953-61.
  • Savarese DM, Savy G, Vahdat L, et al. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev . 2003;29:501-13.