Pharmaconutrition Review: Physiological Mechanisms

Editor(s): Conference Proceedings & Specific Issues Vol.37 / 1,  2013


The search to improve outcomes in critically ill patients through nutrition support has steadily progressed over the past 4 decades. One current approach to this problem is the addition of specific nutrients as primary therapy to improve host defences and improve the outcome of critically ill patients. The field is referred to as “pharmaconutrition,” with the hope of focusing investigations on each nutrient to understand its pharmacological effects on immune and clinical outcomes. The purpose of this review is to describe some of the known physiological mechanisms of pharmaconutrients such as glutamine, arginine, ω-3 fatty acids, and selenium.

Critical illness poses significant challenges to patients who must respond effectively to systemic inflammation, potentially infectious organisms, altered immunity, and metabolic changes resulting in hypermetabolism. The inability to maintain adequate nutrient delivery during these hypercatabolic conditions renders the patient susceptible to significant nutrient deficiencies, which may increase the risk for infection, organ failure, and mortality. Since the ability of patients to meet their needs by eating is usually not possible, the use of nutrition support through parenteral and enteral feeding is frequently employed to provide the required amounts of caloric and nutrient needs. The field of nutrition support has progressed in knowledge and complexity over the past 45 years from simply solving the problem of safely providing enough micronutrients and macronutrients to meet metabolic demands to the current search for individual nutrient regimens to optimize immune function and cell recovery. Initially, the search for specialized formulas focused on enteral products enriched with various combinations of metabolic substrates (e.g. glutamine, arginine, antioxidants, nucleotides, and/or ω-3 fatty acids). The enteral products were referred to as immunonutrition or immune-enhancing diets (IEDs) and were formulations or “cocktails” of nutrients in various concentrations. Since these products contained different combinations of assorted nutrients, the exact contribution of each individual nutrient could not be determined in humans. In 2008, Jones and Heyland suggested we shift the concept of immunonutrition toward a standardized assessment of specific nutrients administered at pharmacological levels, emphasizingan emerging term called pharmaconutrition. This framework suggested nutrients be studied as therapeutic agents administered in physiologic and supraphysiologic (i.e. pharmacologic) doses, thus shifting the focus of specialized nutrition support to a study of active therapeutics and through physiological mechanisms. The difficulty in defining an optimal combination of agents and the optimal dose of each agent remains an impossible task for physiological mechanisms. Nevertheless, it appears that specific pharmaconutrients do improve clinical outcomes in surgical and intensive care unit (ICU) patients and helps through physiological mechanisms.

The concept of pharmaconutrition advocates investigating the effects of pharmacologic doses of individual nutrients on immune function and clinical outcomes, rather than “cocktail” formulations. The various dosages, durations, and efficacy of nutrient supplementation make this an extremely difficult and expensive undertaking, especially given heterogeneous patient populations and the need for a plethora of treatment arms. However, significant clinical evidence suggests that specific nutrients can improve clinical outcomes when provided to the select patient subpopulations or through physiological mechanisms. Updated systematic reviews of the current clinical data and recommendations are available at and http://criticalcarenutri through A.S.P.E.N. and CCCNG, respectively.