Topical Area: Medical Nutrition
Plasma Arginine (Arg) and Glutamine (Gln) are often depleted in early acute illness and sepsis. Treatment methods involving supplementation with one or both amino acids continue to be evaluated for merit. Both Arg and Gln have strong effects on the Area Postrema(AP), a highly vascularized medullary region controlling appetite and nutrient-regulated autophagy. It is plausible that Arg/Gln depletion, observed in acute illness, is a normal physiological sequestration and that supplementation in conjunction with non-protein energy intake (NPEI) counteracts these adaptive responses and healing mechanisms. This study examinesthe current evidence regarding energy intake and Arg/Gln provision in early critical illness.
Methods : Comprehensive review of in vitro, murine, and human interventional studies involving AP lesioning, Arg/Gln turnover measures, and effects of Arg/Glnprovision in acute illness.
Serum Arg/Gln were negatively associated with severity of illness in murine and human studies. In vivoand murine models suggest Arg/Gln contribute to a nutrient-sensing anorectic intracellular relationship with the APduring acute stress. Associated elevations of cytokines TNFα and NF-kB lead to cellular uptake of Arg/Gln, with plasma concentrations of Arg/Gln modulating AP-mediated anorexia. To date, no clinical studies have examined this plausible relationship between nutrition support and AP feedback mechanisms. Human studies, however, have shown that total protein provision, but not Arg/Glnsupplementation, in early critical illness upregulates autophagy and benefits clinical outcomes.
Strong evidence suggests that illness-associated anorexia and the decline in serum Arg/Gln serve as mediators in autophagy and in stimulating repair pathways. The AP appears to regulate these processes and may be negatively impacted by supplementation ofArg/Gln and increased NPEI. Further examination is needed to elucidate the AP-regulated nutrient-sensing appetite mechanisms and the potential effects of total protein intake versus specific amino acids. The labile nature of serum Arg/Glnin acute illness represents a potentially misguided and incomplete point of consideration for stress-state physiology and medical nutrition therapy.
Funding Sources : none.