Antioxidant Therapy, N-acetyl-L-cysteine, Effects on Pancreatic Beta Cells: Therapeutic Promise or Potential Harm?

Abstract

N-acetyl-L-cysteine (NAC) is a widely used antioxidant with increasing public interest in its use for treating metabolic disease, yet its effects on pancreatic beta cells remain incompletely understood. Most studies focus on NAC's benefits under pathological conditions-such as obesity, high-fat diet exposure, and type 2 diabetes-where oxidative stress impairs beta-cell function, identity, and survival. In these contexts, NAC can reduce oxidative damage, preserve insulin secretion, and limit islet fibrosis. However, far fewer studies examine NAC under normal physiological or aging conditions, where moderate reactive oxygen species (ROS) levels are required for beta-cell signaling and glucose-stimulated insulin secretion. Emerging evidence shows that excessive antioxidant exposure during non-pathological states may disrupt redox-dependent pathways, suppress insulin biosynthesis and exocytosis, and contribute to reductive stress. Here, we review the current evidence of NAC's impact on beta cells across physiological, aging, and pathological settings. Moreover, we highlight that NAC can be protective or detrimental depending on redox state, metabolic environment, and dosing, which emphasizes the need for careful consideration of antioxidant use in humans.