Effects of N‐Acetylcysteine on Oxidative Status and Intestinal Health in Piglets ( Sus scrofa domesticus L.): A PRISMA‐Based Systematic Review

Oxidative stress is a critical challenge in intensive swine production, particularly during weaning, compromising intestinal integrity and animal performance. N‐acetylcysteine (NAC) has emerged as a multifunctional nutritional strategy to mitigate these effects due to its role as a glutathione precursor and signaling modulator. This systematic review aimed to critically synthesize the evidence regarding NAC supplementation in piglets, focusing on growth performance, intestinal morphology, antioxidant status, and gut health indicators. A systematic search was conducted on the Web of Science and Scopus databases following PRISMA guidelines. Twenty experimental trials evaluated oral NAC supplementation in suckling and nursery piglets were included. Methodological quality was assessed using the SYRCLE Risk of Bias tool. Results: NAC supplementation consistently improved antioxidant capacity by increasing reduced glutathione (GSH) levels (15% to 40%) and reducing malondialdehyde (MDA) (20% to 35%) across various stress models. In weaned piglets, NAC attenuated pro‐inflammatory signaling (NF‐κB and MAPK pathways), reducing cytokine production (TNF‐α, IL‐1β) and preserving villus height and tight junction expression. In neonatal and intrauterine growth restriction (IUGR) models, NAC promoted mitochondrial biogenesis and bioenergetic rescue. Furthermore, NAC modulated the intestinal microbiota, favoring beneficial genera such as Lactobacillus and Bifidobacterium . Despite these molecular benefits, zootechnical responses were more pronounced under physiological challenges, whereas effects in low‐stress commercial environments remained inconsistent. NAC acts as a physiological modulator that goes beyond simple antioxidant action, providing cytoprotection and maintaining intestinal homeostasis through developmental‐stage‐specific mechanisms.