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Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors

V. Suzanne Klimberg, MD; Alex A. Pappas, MD; Emmanuel Nwokedi; Joseph C. Jensen, MD; J. Ralph Broadwater, MD; Nicholas P. Lang, MD; Kent C. Westbrook, MD
Arch Surg. 1992;127(11):1317-1320. doi:10.1001/archsurg.1992.01420110063013.
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• 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.

(Arch Surg. 1992;127:1317-1320)

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