Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

Table 1

Methods and results of randomized, controlled studies investigating potential beneficial effects of glutamine supplementation in mortality, morbidity, hospital acquired infections, length of stay, or inflammation in endotoxic neonatal animals.

Animal models (pups)	𝑛	Combined with other immunonutrients or inducers	Dose	Route	Duration	Mortality	Hospital- acquired infections	Length of stay	Organ function/Morbidity	Inflammation
Endotoxic 11–13-day-old Wistar rat pups [71]	5	Saline plus LPS plus glutamine	2 mol/kg	Single intraperitoneal injection	90–210 min	—	Improved clinical signs of endotoxic rats	—	—	Restored VO2 of endotoxic animals
Undernourished swiss mice pups/dam [72]	12	Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams	100 mM, 40–80 microL	Daily supplementation with subcutaneous injections	2–14 days	—	—	—	Protects against malnutrition-induced brain developmental impairments	—
Male Wistar suckling rat pups, well-nourished and malnourished during lactation [73]	6–12	No	500 mg/kg/day	By gavage during postnatal days 7 to 27	7 to 27 days	—	—	—	In both nutritional condition, Glutamine rats presented higher cortical spreading depression propagation as compared to water-treated controls	—
Eleven-day rat pups [74]	7–10	Saline plus 300 microg/g Escherichia coli lipopolysaccharide	2 mmol/g	Intraperitoneal injections glutamine	2 or 6 hours	—	—	—	—	TNF𝛼, IL-10 increased by endotoxemia were partly prevented by glutamine
Artificially reared 11 to 13-day-old Wistar rat pups [75]	30	Groups with inhibition of glutamine synthetase by methionine sulfoximine	40 g/kg per day total protein, 10 to 15% of which is glutamine + glutamate, added to a mixture containing carbohydrates, lipids, and vitamins	Artificial feeding using the rat infant “pup in the cup” model through gastrostomy	7–11 days	—	—	—	Glutamine-deprived animals demonstrated breakdown of the epithelial junctions, sloughing of microvilli, decreased actin cores, and degeneration of the terminal	—

LPS: lipopolysaccharide; IL: interleukin; TNF𝛼: tumor necrosis factor alpha; NS: nonstatistical difference.