Although the fasting response has been associated with the activation of beneficial repair pathways in critical illness, prolonged starvation will likely come at the price of devastating sarcopenia and muscle weakness. Therefore, current guidelines rec­ommend to administer full feeding from the second week in the ICU at the latest [49]. However, also in patients with prolonged critical illness and persistent organ failure, repair pathways, including autophagy, are likely important. Yet, the efficacy and safety of macronutrient restriction beyond the first week in ICU have not been studied, and continued starvation for weeks is obviously unwanted. Future studies should investigate whether alternative feeding strategies could activate fasting responses while avoiding prolonged starvation and whether this is clinically supe­rior. In this regard, fasting responses have also been implicated in protection against age-related disease [50]. In this context, the beneficial effects of caloric restriction have been replicated by so-called fasting-mimicking diets [50]. In critical illness, candidate alternative feeding strategies are intermittent fasting, ketogenic diets, or ketone supplementation [ mount a fasting response and associated benefits in critically ill patients remains unclear. A pilot crossover RCT (N = 70) showed that 12 h of fasting induced a metabolic fasting response with increased ketogenesis in prolonged critically ill patients, although autophagy activation in white blood cells was unaf­fected [51]. Whether continued application of intermittent fasting intervals would translate into a clinical benefit remains unclear. RCTs comparing intermittent versus continuous feeding have shown mixed results [52, 53]. However, most RCTs were relatively small, and the fasting interval in these studies (generally only 4 to 6 h) may have been too short to impact the outcome beneficially [41].