Oxidative Stress, Iron Dysmetabolism and Ferroptosis: Emerging Dietary Targets in MASLD: Nutrition Research | August 2026

Introduction:

Oxidative stress and abnormal hepatic iron metabolism are increasingly recognized as interconnected drivers of progression from steatosis to MASH and fibrosis. This review proposes an “oxidative stress–iron dysmetabolism axis”, with ferroptosis acting as an important downstream mechanism, and explores whether targeted dietary interventions can interrupt this cycle.

Why was this review needed?

Oxidative stress is central to metabolic liver injury and fibrosis progression.

Approximately one-third of affected patients may demonstrate evidence of hepatic iron overload.

Iron excess and reactive oxygen species (ROS) can amplify each other, promoting lipid peroxidation and hepatocyte injury.

Current dietary recommendations focus mainly on weight loss rather than specific molecular pathways.

Key Takeaways:

Iron overload increases ROS through the Fenton reaction, while oxidative stress further disrupts hepcidin–ferroportin regulation, creating a self-perpetuating cycle.

This interaction promotes lipid peroxidation and ferroptosis, contributing to hepatocyte injury, inflammation, and fibrosis.

Dietary strategies may interrupt this pathway by activating antioxidant defenses such as Nrf2/GPX4, improving iron homeostasis and reducing ferroptosis.

Potential approaches include healthier dietary patterns, polyphenols and other bioactive compounds, selected nutrients, omega-3 fatty acids, and probiotics, although the strength of clinical evidence varies substantially.

Translation into clinical practice remains limited because most evidence is mechanistic or preclinical, and optimal interventions and patient selection remain uncertain.

Clinical Impact:

This review moves dietary therapy beyond simple calorie restriction and weight loss toward the concept of mechanism-based nutritional intervention. Oxidative stress, iron metabolism, and ferroptosis may eventually help identify patients who benefit from more personalized dietary strategies. However, these approaches should currently complement—not replace—established lifestyle and pharmacological management.

Bottom Line:

Oxidative stress and iron dysmetabolism form a vicious cycle that may drive metabolic liver disease through ferroptosis. Targeting this axis through personalized nutrition is biologically attractive, but robust human trials are needed before specific antioxidant or iron-modulating dietary interventions can be recommended routinely.