**12. Metabolite supplements for restoring homeostasis during PN**

PN is required in patients with progressive malnutrition, which is exacerbated by infectious and injurious challenge, leading to hypermetabolism. A major goal of recent research has been to find combinations of PN additives that will reduce the detrimental impact on the gut's immune and metabolic functions, as well as on the mucous composition in the intestinal and respiratory tract. Immune enhancing nutrition formulations include the addition of glutamine, arginine, cysteine, tyrosine, leucine, choline, ω-3 fatty acids, nucleotides, and micronutrients (vitamin C, selenium, and tracer elements including iron and zinc). Glutamine has been studied most extensively as the most prominent free amino acid that supports normal metabolism but becomes limited during gut atrophy and critical illness [134]. Recent reviews have concentrated on the effects of these additives in basic and clinical work [135]. Outside of macronutrients classes, targets that stimulate aspects of immune and neuronal signaling have promise in mediating elevated immune and barrier response when PN is necessary.
