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In addition to being the major fuel source for rapidly proliferating intestinal and immune cells, L-GIn is also the main fuel source for many rapidly growing tumours and as a result tumour growth is associated with a depletion in glutamine and glutathione stores and a depression of NK cell activity (Fahr et al 1994, Miller 1999). The increased intestinal permeability, immune suppression and oxidative damage that may result may further compromise the body's ability to deal with the tumour. While concerns exist, and are supported by in vitro evidence, that glutamine supplementation may feed the tumour, animal studies suggest that glutamine supplementation may assist in decreasing tumour growth by enhancing NK cell activity (Fahr et al 1994, Miller 1999). Animal studies have demonstrated that glutamine supplementation prevents the promotion of tumour cells in an implantable breast cancer model (Kaufmann et al 2003). The exact effects in different human tumour cell lines require further elucidation.

Clinical note — Cancer therapy

Side-effects of chemotherapy and radiation therapy can significantly affect the QOL of patients undergoing treatment for cancer. A number of trials have demonstrated the benefits of glutamine supplementation for improving side-effects such as oral pain and inflammation, increased gut permeability and reduced lymphocyte count.

Reduced oral pain and Inflammation has been observed in patients receiving radiation and chemotherapy during bone marrow transplantation taking 1 g glutamine four times daily (Miller 1999). In another study, L-GIn (4 g twice daily, swish and swallow) was given to 12 patients receiving doxorubicin, 1 receiving etoposide, and 1 receiving ifosfamide, etoposide, and carboplatinum from day 1 of chemotherapy for 28 days or for 4 days past the resolution of any post-chemotherapy mucositis. Oral supplementation with glutamine significantly decreased the severity of chemotherapy-induced stomatitis (Skubitz & Anderson 1996).

In one report, L-GIn (10 g three times daily), given 24 hours after receiving paclitaxel, appeared to prevent the development of myalgia and arthralgia associated with treatment (PDRHealth 2006a).

In a double-blind, placebo-controlled, randomised trial, oral glutamine (18 g/day) or placebo was given to 70 chemotherapy naive patients with colorectal cancer 5 days prior to their first cycle of 5-fluorouracil (5-FU) (450 mg/m2) in association with folinic acid (FA) (100 mg/m2), which was administered intravenously for 5 days. Glutamine treatment was continued for 1 5 days and was shown to reduce the negative effects on intestinal absorption and permeability induced by the chemotherapy and to potentially reduce diarrhoea (Daniele et al 2001 ). l-glutamine may also reverse the decrease in goblet cells induced by 5-FU (Tanaka & Takeuchi 2002).

Yoshida et al (1998, 2001 ) have also shown that 30 g/day L-GIn for 28 days attenuates the increased gut permeability and reduced lymphocyte count observed in patients undergoing cisplatin and 5-FU therapy for oesophageal cancer.

Glutamine may also increase tumour methotrexate concentration and tumoricidal activity and reduce side-effects and mortality rates (Miller 1999, PDRHealth 2006a)._

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