Table 7.

Enteral glutamine supplementation in chronic diseases of childhood.

Reference	Subjects	Design	Gln	Control	Outcomes	Results
Hankard et al. 1998 [204]	6 DMD boys aged 8–13 y	Time series	Study d-2: oral Gln (0.6 g/kg) dissolved in flavoured water (Kool-Aid) given over 5 h (n = 6)	Study d-1: oral flavoured water (Kool-Aid) given over 5 h (n = 6)	Whole body protein and Gln metabolism (IV infusion of L-[1–13C]Leu and L-[2–15N]Gln) in postabsorptive state (14 h fast) while drinking placebo on d-1 and Gln supplement on d-2, plasma AA concentrations	Decreased Leu release from protein breakdown and Leu oxidation rate, no effect on nonoxidative Leu disposal (an index of protein synthesis), increased whole-body Gln exchange in plasma, decreased Gln from protein degradation and Gln de novo synthesis, increased plasma Gln concentration, decreased plasma concentrations of essential AA (Leu, Phe, Lys)
Escolar et al. 2005 [206]	35 ambulant steroid-naive DMD boys aged 4–10 y	Randomized double-blind multicentre	Oral Gln (0.3 g/kg/d BID) for 6 mo (n = 19)	Placebo for 6 mo (n = 16)	Efficacy as assessed by changes at 6 mo in: (1) average manual muscle testing score, quantitative muscle-testing, (2) timed functional tests, pulmonary function tests, and safety	(1) No effect on manual or quantitative measurements of muscle strength, (2) young age (<7 y) subgroup showed less deterioration in timed functional tests, but no differences for entire cohort or for old age (≥7 y) subgroup, safe, and well tolerated
Mok et al. 2006 [205]	26 DMD boys aged 7–15 y	Randomized double-blind	Oral Gln (0.5 g/kg/d) given as powder mixed with yogurt for 10 d (n = 13)	Oral isonitrogenous nonspecific AA mixture given as powder mixed with yogurt for 10 d (n = 13)	Whole-body protein and Gln metabolism (IV infusion of L-[1–13C]Leu and L-[2–15N]Gln) in postabsorptive state after 10 d supplementation, body composition (BIA and 3-d urinary creatinine excretion), plasma concentrations of AA	Decreased rate of Leu appearance (an index of whole-body protein degradation) and endogenous Gln from protein degradation (both groups), no effect on Leu oxidation rate, nonoxidative Leu disposal (an index of protein synthesis), whole-body Gln exchange in plasma, Gln de novo synthesis or plasma Gln concentrations, no effect on fat-free mass, % fat mass, muscle mass or wt, safe, and well tolerated
Mok et al. 2009 [209]	30 ambulant DMD boys aged 2–10 y	Randomized double-blind crossover multicentre	Oral Gln (0.5 g/kg/d) for 4 mo (n = 30)	Oral placebo (maltodextrin) for 4 mo (n = 30)	Efficacy as assessed by changes at 4 mo in: (1) walking speed, (2) 2-minute walk test, work, power, muscle mass (urinary creatinine), myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phosphokinase, % fat mass, fat-free mass (BIA), safety	No differences in measures of function: (1) walking speed, (2) 2-minute walk test, work or power, but steroid-treated subgroup showed less deterioration in functional measures during Gln phase, no differences in muscle mass, myofibrillar protein breakdown, or serum creatine phosphokinase, increased % fat mass, blunted increase in fat-free-mass, safe, and well tolerated,
Williams et al. 2004 [222]	27 children aged 5.2–17.9 y with sickle cell anemia	Case series	Oral Gln supplement (0.3 g/kg/d BID) for 24 wk	None	Measures of REE (indirect calorimetry/Harris Benedict equation) and other nutritional parameters after 24 wk supplementation	Decreased median REE overall with greater decrease in underweight (<90% IBW) subgroup, increased BMI, %FM and handgrip strength, increased plasma concentrations of Gln and Trp
Darmaun et al. 2004 [225]	9 prepubertal children aged 7–13 y with cystic fibrosis; undernourished (wt/height <50% ile) or short (height <5% ile)	Time series (order of Gln and rhGH regimens randomized)	4-wk supplementation with: (1) oral Gln (0.7 g/kg/d), (2) SC rhGH and (3) Gln + rhGH combined	Baseline	Whole-body protein and Gln metabolism (IV infusions of H13CO3Na, L-[1–13C]Leu and L-[2–15N]Gln) in postabsorptive state (after 12 h fast) after 4-wk treatment, body composition (skinfold thickness, BIA, DXA), plasma concentrations of glucose, hormones, growth factors, and AA	No effect on Leu release from proteolysis, Leu oxidation, or nonoxidative Leu disposal (an index of protein synthesis), no effect on Gln appearance rate, Gln release from proteolysis, or Gln de novo synthesis, increased plasma Gln concentrations, increased lean body mass, no effect on glucose metabolism
Mauras et al. 2010 [229]	10 type 1 diabetic adolescents on insulin pumps; mean ± SD age: 15.2 ± 1.4 y	Randomized double-blind crossover	Oral Gln drink before exercise and at bedtime (0.25 g/kg/dose) (n = 10)	Oral placebo drink (calorie and nitrogen free) before exercise and at bedtime (n = 10)	Blood glucose % drop from baseline during exercise, hypoglycemia during exercise, postexercise overnight hypoglycemia, cummulative probability of postexercise overnight hypoglycemia	During exercise, no differences in blood glucose % drop from baseline or proportion that develop hypoglycemia, increased postexercise overnight frequency of hypoglycemic events, increased cummulative probability of postexercise overnight hypoglycemia

DMD: Duchenne muscular dystrophy; IV: intravenous; AA: amino acid; BID: twice a day; BIA: bioelectrical impedance analysis; wt: weight; REE: resting energy expenditure; IBW: ideal body weight; BMI: body mass index; FM: fat mass; rhGH: recombinant growth hormone; SC: subcutaneous; DXA: dual X-ray absorptiometry.