The Role of Nutrients in Modulating Neuroinflammation: A Systematic Review of Preclinical and Clinical Studies

Neuroinflammation is increasingly recognized as a central mechanism underlying the initiation and progression of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Chronic activation of microglia, dysregulation of inflammatory cytokine signaling (e.g., TNF-α, IL-1β, IL-6), activation of NF-κB pathways, and NLRP3 inflammasome assembly contribute to synaptic dysfunction, neuronal loss, and cognitive decline. Emerging evidence suggests that metabolic and nutritional factors play a critical role in modulating these neuroimmune pathways. Specific nutrients—including omega-3 polyunsaturated fatty acids (PUFAs), ketogenic dietary interventions, B vitamins, vitamin D, and microbiota-targeted strategies—have been proposed as modulators of neuroinflammatory processes. However, the mechanistic coherence and translational relevance of these interventions across experimental and clinical contexts remain incompletely synthesized. This project aims to systematically evaluate and integrate preclinical and clinical evidence examining how nutritional interventions influence neuroinflammatory mechanisms relevant to AD and MCI.