Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies
Table 2
Methods and short-term results of randomized, controlled studies investigating potential beneficial effects of glutamine supplementation in mortality, morbidity, hospital-acquired infections, length of stay, or inflammation in premature infants.
Isonitrogenous study amino acid solution with 20% glutamine
Early parenteral nutrition
120 days
NS
NS
NS
Increased plasma Glutamine concentrations but also more days of PN support. No differences of late onset sepsis, NEC, day to first and full enteral feeds, feeding intolerance, or growth
—
Premature infants ≤32 weeks gestation with a birth weight from 694 to 1590 g [77]
20
No
0.6 g/kg/day
Early parenteral nutrition with amino acid intake 3.0 g/kg/day for at least 3 days
Tracer isotope studies at 6 to 7 days old
—
—
—
Supplemental glutamine was associated with a lower rate of appearance of glutamine, phenylalanine, and leucine C. No difference in leucine N and urea turnover
No significant difference in plasma cortisol and C-reactive protein levels
Decreased rates of Leu release from protein breakdown and Leu oxidation, decreased rates of nonoxidative Leu disposal (an index of whole-body protein synthesis), safe
Isonitrogenous amino acid solution with 20% of the total amino acids as glutamine
Parenteral glutamine supplementation on plasma amino acid concentrations
10 days
—
—
—
No significant difference between the 2 groups in the relative change in plasma glutamate concentration but significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples
VLBW age < 7 d receiving PN; birth wt: 500–1250 g [87]
649
No
0.3 g/kg/day
Within the first 7 d of age, randomly assigned to enteral glutamine supplement (3% glutamine in sterile water) or placebo (sterile water) given at the same time but separate from feedings
7 days–36 weeks post menstrual age
NS
NS
NS
Less gastrointestinal dysfunction, severe neurological sequelae among survivors (grades 3 and 4 intraventricular hemorrhage and paraventricular leukomalacia) in glutamine group. No difference in NEC, retinopathy of prematurity, oxygen use at 36 weeks, or growth,
—
VLBW infants < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [88]
102
No
Increasing doses from day 3–30 of life to a maximum dose of 0.3 g/kg/day
Glutamine-enriched isonitrogenous enteral nutrition added to breast milk or preterm formula
Day 3–30 of life
NS
Lower incidence of ≥1 serious infections
NS
No difference in feeding tolerance, NEC, or growth, patent ductus arteriosus, mechanical ventilation, supplemental oxygen, retinopathy
—
VLBW < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [89]
86
No
Increasing doses to ≤0.3 g/kg/day
Enteral preterm formula or breast milk supplemented with Glutamine or isonitrogenous Ala
Day 3–30 of life
NS
NS
—
No difference in prevalence of intestinal microflora (bifidobacteria, lactobacilli, Escheria coli, streptococci, clostridia) at <48 h–d30 of life, by fluorescent in situ hybridization
—
VLBW < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [90]
90
No
Increasing doses to ≤0.3 g/kg/day
Enteral preterm formula or breast milk supplemented with glutamine or isonitrogenous Ala
Day 3–30 of life
NS
NS
—
No difference in decreased lactulose/mannitol ratio or urinary lactulose or increased urinary mannitol concentrations
—
VLBW infants <48 h after birth receiving PN; birth wt: < 1500 g; GA < 32 wk [91]
63
No
Increasing doses to ≤0.3 g/kg/day
Enteral preterm formula or breast milk supplemented with glutamine or isonitrogenous Ala
Day 3–30 of life
NS
NS
—
—
No differences in Th1 or Th2 cytokine responses at 48 h–d 14 of life following in vitro whole blood cell stimulation