Pharmaconutrition: The End of an Era?

Abstract

Pharmaconutrition has been an interesting area of research in critical care. Initially, trials with high dose glutamine and/or selenium reported promising outcomes but were often underpowered. Notwithstanding, systematic reviews and meta-analyses conducted up to 2015 found significant reductions in infection and/ or mortality rates in the critically ill. However, later meta- analyses have not shown improvement in clinical outcomes. Consequently, current guidelines do not make any recommendations for high dose nutrient therapy. Is this the end of the pharmaconutrition era? Not necessarily! It is time to return to basics and adopt a more pharmaceutical approach by categorising pharmaconutrients as drugs; better establish their in vitro and in vivo stability, pharmacology, toxicology and safety, then determine any drug-drug or drug-nutrient interactions before proceeding to pharmacokinetics and pharmacodynamics studies. We must additionally investigate the true nature of nutrient deficiency in the critically ill. How different is a deficiency in a naturally low Selenium population versus a ‘normal’ population? What happens to a high dose of a synthetic glutamine dipeptide in a nutrient deficient patient, or
one with organ failure, and what happens to the excess pharmaconutrient that is not utilised by a nutritionally replete patient?
These basic questions were inadequately investigated in the past, where fixed supraphysiological doses were administered to all patients, a significant proportion of whom were not nutrient deficient. When quality data have been generated on these preclinical parameters, we can more accurately determine indications, optimum posology and better guidelines for new clinical investigations and begin a new era of Pharmaceutical Nutrition.