Molecular Mechanisms of Pharmaconutrients

Abstract

Nutritional supplementation has become the standard of care for management of critically ill patients. Traditionally, nutritional support in this patient population was intended to replete substrate deficiencies secondary to stress-induced catabolism. Recognition of the influence of certain nutrients on the immune and inflammatory response of the critically ill has led to the evolution of more sophisticated nutritional strategies and concepts. Administration of immune-enhancing formulas supplemented with a combination of glutamine, arginine, omega-3 fatty acids and nucleotides have been shown in most studies to reduce infectious outcomes. More recently, the separation of nutritional support from the provision of key nutrients, has led to a further appreciation of the immunomodulatory and anti-inflammatory benefits of isolated nutrients, such as glutamine and antioxidants. The purpose of this article is to review the molecular mechanisms that are unique to each class of frequently utilized nutrients. A better understanding of the specific molecular targets of immunonutrients will facilitate application of more refined nutritional therapies in critically ill patients.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…However, arginine supplementation could lead to unwanted vasodilation and hypotension [619,620]. Human trials of l-arginine supplementation have generally been small and reported variable effects on mortality [621][622][623][624]. The only study in septic patients showed improved survival, but had limitations in study design [623].…”

“…The only study in septic patients showed improved survival, but had limitations in study design [623]. Other studies suggested no benefit or possible harm in the subgroup of septic patients [621,624,625]. Some authors found improvement in secondary outcomes in septic patients, such as reduced infectious complications) and hospital LOS, but the relevance of these findings in the face of potential harm is unclear.…”

Immunonutrition: a South African perspective

“…81 The anti-inflammatory properties occur through three principle mechanisms: displacement of arachidonic acid in cell membranes, prostaglandin E3 and LTB4 production, decreased nuclear factorkappa B (NF-κB) and AP-1 activation. 81 Omega-3 FAs (ω-3 FAs) have also been shown to decrease the production of nitric oxide (NO) via downregulation of iNOS protein expression.…”

“…81 The anti-inflammatory properties occur through three principle mechanisms: displacement of arachidonic acid in cell membranes, prostaglandin E3 and LTB4 production, decreased nuclear factorkappa B (NF-κB) and AP-1 activation. 81 Omega-3 FAs (ω-3 FAs) have also been shown to decrease the production of nitric oxide (NO) via downregulation of iNOS protein expression. 81,82 Although the inclusion of ω-3 FAs in nutrition therapy makes theoretical sense and the potential mechanisms are fairly clear, the data for the implementation of such nutrient therapy in critically ill patients are much less concrete.…”

“…81 Omega-3 FAs (ω-3 FAs) have also been shown to decrease the production of nitric oxide (NO) via downregulation of iNOS protein expression. 81,82 Although the inclusion of ω-3 FAs in nutrition therapy makes theoretical sense and the potential mechanisms are fairly clear, the data for the implementation of such nutrient therapy in critically ill patients are much less concrete.…”