Glutamine Supplementation in Sick Children: Is It Beneficial?

Table 5

Glutamine supplementation in pediatric oncology patients.

Reference	Subjects	Design	Gln	Control	Outcomes	Results
Anderson et al. 1998 [180]	193 patients aged 1–62 y (72 children aged 1–18 y) undergoing BMT	Randomized double-blind	Enteral Gln; oral Gln suspension 1 g AA/m2 QID administered from admission until 28 d after BMT (𝑛=98; 34 children)	Oral Gly suspension 1 g AA/m2 QID administered from admission until 28 d after BMT (𝑛=95; 38 children)	(1) Severity and duration of stomatitis by self-report and by opiate use at d7, d14, and d28 after BMT, (2) PN use, rate of relapse or progression of malignancy, parental antibiotic use, acute or chronic GVHD, LOS in hospital, bacterial, or fungal infections, survival, and Gln toxicity during d0–d28 after BMT in patients prospectively stratified by type of transplant (autologous, matched sibling donor, or unrelated donor)	For autologous BMT: (1) reduced severity of oral mucositis by self report and reduced opiate use; for matched sibling BMT: no effect on severity of oral mucositis by self report, increased opiate use and (2) increased % survival at d28; for autologous or allogeneic BMT: no differences in PN use, rate of relapse or progression of malignancy, antibiotic use, acute or chronic GVHD, LOS in hospital, infections or survival, safe
Anderson et al. 1998 [179]	13 cancer patients (10 children aged 4–17 y) receiving chemotherapy	Randomized double-blind crossover	Enteral Gln; oral Gln suspension 2 g AA/m2 BID during chemotherapy and for ≥14 d after chemotherapy (𝑛=13; 10 children)	Oral Gly suspension 2 g AA/m2 BID during chemotherapy and for ≥14 d after chemotherapy (𝑛=13; 10 children)	Patient self-report of onset, duration, and severity of stomatitis over each chemotherapy course, as assessed by a questionnaire/calendar completed by the patient	Decreased number of d of mucositis, reduced severity (decreased number of d of oral mucositis ≥ Grade 2; Modified Eastern Cooperative Oncology Group, requiring restricted oral intake to soft foods), well tolerated
Pietsch et al. 1999 [175]	17 children aged 2–19 y receiving intensive chemotherapy (𝑛=14) or BMT (𝑛=3)	Case series	Enteral Gln; continuous nasogastric feedings of Gln-supplemented elemental EN (Vivonex Pediatric) during chemotherapy and at rehospitalization for ~12.7 d	None	Feasibility (hospital costs and complications)	Well-tolerated, lower hospital charges for enteral feedings compared to the same number of d of PN
Ward et al. 2003 [176]	13 pediatric patients aged 3–18 y undergoing treatment for malignancy	Phase 1 pharmaco-kinetic (initial dose-finding study)	Enteral Gln; oral Gln (mixed with sterile water) administered as 1 dose starting at 0.35 g/kg and increased by increments of 0.15 g/kg if 3 patients at each dose level tolerated the Gln	None	Patient acceptability and safety as assessed by measurement of plasma concentrations of Gln and ammonia at 60, 90, 120, 240, and 360 min after a single dose of Gln	Well tolerated and safe at 0.35, 0.5, and 0.65 g/kg; at 0.65 g/kg: plasma Gln and ammonia peaked between 30 and 90 min and returned to normal by 360 min post-Gln
Aquino et al. 2005 [178]	120 children [mean age (y)±SEM: 8.9±1.0 (Gln) and 10.5±0.6 (Gly)] undergoing HSCT	Randomized double-blind	Enteral Gln; oral Gln 2 g/m2/dose BID (maximum dose 4 g) until 28 d posttransplant or discharge (𝑛=57)	Oral Gly 2 g/m2 BID (maximum dose 4 g) until 28 d posttransplant or discharge (𝑛=63)	(1) Oral mucositis graded by modified Walsh Scale, (2) maximum mucositis score, d of IV narcotic use, d of PN use, ≥1 episodes of bacteremia, LOS in hospital, mortality, and toxicity until discharge or until 28 d posttransplant	(1) Trend toward a reduction in mean mucositis score, (2) no difference in maximum mucositis score, reduced number of d of IV narcotic use, reduced d of PN, no differences in number of episodes of bacteremia, LOS in hospital or mortality, safe, and well tolerated
Okur et al. 2006 [181]	21 children aged 1–17 y with solid tumors receiving chemotherapy	Time series	Enteral Gln; oral Gln 2 g/m2/d BID during 5 d chemotherapy course (𝑛=21)	The same protocol without Gln supplementation during another 5 d chemotherapy course (𝑛=21)	Immunologic, nutrition, and anthropometric parameters after 5 d course of chemotherapy, stomatitis, and antibiotic use	Decreased lymphocyte count, increased complements 3 and 4, increased prealbumin and transferrin, no differences in anthropometric parameters, reduced stomatitis, and antibiotic use
Kuskonmaz et al. 2008 [177]	41 pediatric patients [mean age (y)±SEM: 8.3±5.2 (Gln) and 6.9±4.3 (control)] who underwent HSCT	Case control	Parenteral Gln; IV Gln (0.4 g/kg/d) for ~13 d with or without PN (𝑛=21)	Controls were elected from presupplemented period and matched to cases with respect to donor type, diagnosis, and age	Mucositis (grades 3 and 4), PN use, neutrophil engraftment, incidence and duration of fever, documented infections, acute GVHD, sinusoidal obstruction syndrome, drug-related toxicity, LOS in hospital, and mortality	Nonsignificant trend toward reduced mucositis, sinusoidal obstruction syndrome and drug-related toxicity, reduced duration of fever, no differences in PN use, neutrophil engraftment, infections, acute GVHD, LOS in hospital or mortality, safe

BMT: bone marrow transplant; AA: amino acid; QID: 4 times a day; PN: parenteral nutrition; GVHD: graft versus host disease; LOS: length of stay; BID: twice a day; EN: enteral nutrition; SEM: standard error of the mean; HSCT: hematopoietic stem cell transplant; IV: intravenous.