Ferroptotic neurodegeneration and diet: a narrative review

The neuroprotective potential of various dietary interventions has emerged as a complementary approach to delay neurodegeneration. Ferroptosis, a mechanism of cell death, may be influenced by dietary interventions. Ferroptosis is driven by labile iron generating reactive oxygen species, resulting in lipid peroxidation and cellular death. Iron accumulates in the brain in various neurodegenerative disorders, and this correlates with disease progression.

We reviewed studies reporting effects of dietary interventions on brain iron accumulation and/or ferroptosis.

We report indications that dietary interventions can impact ferroptosis in the brain. Anti-ferroptotic effects involve reduced lipid peroxidation, enhanced antioxidant defense activity, and reduced labile iron through altered iron metabolism. Transcription factor Nrf2 may be the core regulator of dietary anti-ferroptotic effects, connecting the three pathways of ferroptosis.

Targeting ferroptosis through diet may offer a feasible approach to supporting brain health across neurodegenerative conditions, but dedicated studies are required to directly investigate this potential.