What Are We Actually Feeding ICU Patients? The Case for Studying Formula Composition

Large randomized controlled trials testing the quantity and timing of enteral nutrition (EN) in critically ill patients have consistently failed to demonstrate benefit. We propose that these negative results may partly reflect an unexamined variable: the composition of EN formulas themselves. Most widely used formulas rely on corn-derived simple carbohydrates, isolated functional fibers, dairy-based proteins, and omega-6-rich vegetable oils, ingredients selected largely for manufacturing efficiency and shelf stability rather than clinical evidence. These components bear little resemblance to whole foods, and their distinct effects on metabolism, inflammation, and gut function have received little study in critical illness. Commercially available whole-food and plant-based EN formulas now offer compositionally distinct alternatives, yet no rigorous trials have compared them to conventional formulas in critically ill patients. We argue for a paradigm shift from volume-based to composition-focused nutrition research, pairing patient-centered clinical outcomes with mechanistic endpoints, including effects on the gut microbiome.