Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (−GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0±0.20 nmol/g for the +GLN group vs 28.8±0.10 nmol/g for the −GLN group and 35.6±0.18 nmol/g for the +GLN group vs 32.5±0.16 nmol/g for the −GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147±0.007 μm/L for the +GLN group vs 0.120±0.006 μm/L for the −GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (−2.41±1.3 cm³ for the +GLN group vs −0.016±0.9 cm³ for the −GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 ±0.13 μmol/g per hour for the +GLN group vs 1.47±0.22 μmol/g per hour for the −GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.