This narrative review examines the evidence and mechanisms behind the lack of benefit and potential harm of early full nutritional support in critically ill patients. Recent randomized controlled trials (RCTs) have shown that early full nutritional support, regardless of the route, does not provide benefits and may even cause harm, particularly in the acute phase of critical illness. The harm is attributed to anabolic resistance, suppression of cellular repair processes, and increased hyperglycemia and insulin needs. High doses of individual macronutrients, including amino acids, have also been found to be harmful. However, most studies focus on interventions initiated within the first week after ICU admission, and there is a lack of large RCTs studying interventions beyond this period. The review discusses the impact of these findings on clinical practice and guidelines, noting that international guidelines have shifted towards more restrictive nutrition practices in the acute phase. The review also highlights the challenges in monitoring anabolic resistance and the potential risks of prolonged underfeeding. Future research should focus on interventions initiated beyond the acute phase and explore the use of indirect calorimetry and metabolic monitors to guide nutritional therapy. Additionally, the review suggests that personalized medical nutrition therapy is desirable but currently feasible due to the lack of validated tools to monitor actual needs. The review concludes by emphasizing the need for further research to optimize nutritional strategies in critically ill patients.This narrative review examines the evidence and mechanisms behind the lack of benefit and potential harm of early full nutritional support in critically ill patients. Recent randomized controlled trials (RCTs) have shown that early full nutritional support, regardless of the route, does not provide benefits and may even cause harm, particularly in the acute phase of critical illness. The harm is attributed to anabolic resistance, suppression of cellular repair processes, and increased hyperglycemia and insulin needs. High doses of individual macronutrients, including amino acids, have also been found to be harmful. However, most studies focus on interventions initiated within the first week after ICU admission, and there is a lack of large RCTs studying interventions beyond this period. The review discusses the impact of these findings on clinical practice and guidelines, noting that international guidelines have shifted towards more restrictive nutrition practices in the acute phase. The review also highlights the challenges in monitoring anabolic resistance and the potential risks of prolonged underfeeding. Future research should focus on interventions initiated beyond the acute phase and explore the use of indirect calorimetry and metabolic monitors to guide nutritional therapy. Additionally, the review suggests that personalized medical nutrition therapy is desirable but currently feasible due to the lack of validated tools to monitor actual needs. The review concludes by emphasizing the need for further research to optimize nutritional strategies in critically ill patients.