Chlorogenic Acid in Brain Health and Cognitive Resilience: Neuroprotective Mechanisms, Evidence, and Translational Perspectives

Abstract

Chlorogenic acid (CGA), a phenolic ester formed between caffeic acid and quinic acid, is one of the most abundantly consumed dietary polyphenols, found in high concentrations in green coffee beans, various fruits, and vegetables. Over the past two decades, a substantial body of preclinical and emerging clinical evidence has converged on the view that CGA possesses meaningful neuroprotective and cognitive-enhancing properties. This narrative review synthesises current knowledge on the effects of dietary CGA on learning, memory, and cognitive resilience, with particular emphasis on its underlying neurobiological mechanisms. Evidence reviewed includes in vitro studies, rodent behavioural paradigms, and human interventional trials. CGA exerts its neuromodulatory actions through multiple convergent pathways, including attenuation of oxidative stress via Nrf2/HO-1 signalling, suppression of neuroinflammatory cascades via NF-κB inhibition, upregulation of the cAMP/PKA–CREB–BDNF axis supporting synaptic plasticity, inhibition of acetylcholinesterase activity, and modulation of the gut–brain axis. Preclinical models of Alzheimer's disease, ischaemia, diabetes-associated cognitive decline, and scopolamine-induced amnesia consistently demonstrate CGA-mediated improvements in spatial, recognition, and aversive memory. Human evidence, while still limited by small sample sizes and heterogeneous designs, points to improvements in attention, executive function, and episodic memory following sustained CGA intake. Bioavailability constraints remain a principal translational challenge, with extensive colonic biotransformation limiting systemic exposure of intact CGA. The review concludes by identifying critical gaps, including the need for well-powered randomised controlled trials, standardised dosing protocols, and investigations in vulnerable populations. On current evidence, CGA represents a promising dietary candidate for supporting cognitive resilience, though this conclusion rests predominantly on preclinical data and should be regarded as hypothesis-generating pending larger, controlled human trials.