Neurobiochemical Effects of a High-Fat Diet: Implications for the Pathogenesis of Neurodegenerative Diseases

The global rise in high-fat diet (HFD) consumption and obesity has raised concerns about their long-term effects on brain health. This review addresses how HFDs, including ketogenic diets (KDs), influence the central nervous system (CNS) and may contribute to neurodegenerative processes. The findings show that prolonged HFD exposure is associated with altered brain metabolism, increased oxidative stress, neuroinflammation, and impaired synaptic plasticity, particularly in regions like the hippocampus and hypothalamus. These changes may affect cognitive function and accelerate neurodegenerative mechanisms linked to disorders such as Alzheimer's and Parkinson's disease. While certain types of KD appear to exert neuroprotective effects-such as improved motor outcomes in experimental Parkinson's disease models-evidence remains inconsistent, and concerns about their long-term safety persist. This review emphasizes that the impact of high-fat nutrition on the CNS depends on fat type, exposure duration, and individual factors such as age and sex. Overall, further research is needed to distinguish between harmful and potentially therapeutic dietary fat patterns and to better understand their influence on brain health across the lifespan.