Daniele, B., Perrone, F., Gallo, C., Pignata, S., De Martino, S., De Vivo, R., … D'Agostino, L. (2001). Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut, 48(1), 28–33.

To evaluate the effect of glutamine on intestinal absorption and permeability in patients with colorectal cancer

Patients receiving their first cycle of chemotherapy with 5-fluorouracil (5-FU) and folinic acid (FA) for five days were randomly assigned to receive either 18 g glutamine or placebo for 15 consecutive days, beginning 5 days before chemotherapy initiation. The experimental dose (18 g) was much greater than the normal dietary intake (1 g).
 

This study reported on 70 patients with colorectal cancer who were chemotherapy naïve. 

This was a randomized, double blind, placebo-controlled, two armed, parallel trial.

Intestinal absorption (IA) was measured using d-xylose absorption test and intestinal permeability (IP) using cellobiose-mannitol permeability test.  Both of these tests have been confirmed to be reliable and sensitive in clinical conditions characterized by disruption of the normal small intestinal mucosa (e.g., celiac disease, Crohn’s disease).

• For both groups, chemotherapy induced worsening of IA and IP. When pretreatment IA was compared to post-treatment IA, reduction in IA was significantly greater in the placebo group (p = 0.02).
• The placebo group experienced a higher incidence of diarrhea, but this was not statistically significant (p = 0.09).
• The placebo group used significantly more loperamide (p = 0.002). No differences were found in episodes of nausea, vomiting, or hematologic toxicity.
   

Glutamine was shown to reduce changes in IA and IP during 5-FU chemotherapy and may have a protective effect against diarrhea by enhancing the barrier function of the intestine.

• The sample size needed for statistical analysis was 70, but only 62 patients were included in the final analysis.
• The findings are applicable to chemotherapy using 5-FU and FA only.

This study used sensitive and reliable tests to evaluate the morphological changes to the intestine that are casually related to diarrhea incidence. The results are consistent with previous studies that have demonstrated the protective effects of glutamine on the intestinal mucosa.