Magnesium and Brain Health across the Lifespan: A Multilevel Review of Nutritional Sources and Molecular Mechanisms Underlying Cognitive Resilience

Abstract

Aging, neurodegenerative disorders, metabolic disorders, and chronic inflammation are all conditions that are linked to cognitive dysfunction, making it a major health problem worldwide. The mineral magnesium, Mg²⁺, is essential for a variety of enzymatic processes and is known to be crucial in neuronal functions, synaptic plasticity, energy metabolism, and cognitive processes. This review aims to provide a summary of the current evidence on dietary, marine and microbial, as well as supplemental sources of magnesium, focusing on magnesium bioavailability, brain magnesium homeostasis and molecular mechanisms involved in cognitive resilience. There are several ways in which magnesium supports brain health, such as regulating the activity of the N-methyl-D-aspartate (NMDA) receptor, supporting calcium homeostasis, supporting mitochondrial ATP production, and regulating oxidative stress and neuroinflammation. It also affects intracellular signaling, specifically ERK–CREB–BDNF signaling, that are crucial for the processes of neurogenesis, synaptic remodeling and memory formation. Evidence also continues to grow of interactions between magnesium, gut–brain axis and neuroimmune regulation. The specific importance of magnesium deficiency is supported by consistent preclinical findings of impaired synaptic function, neuroinflammation and cognitive dysfunction, while magnesium supplementation has been demonstrated to be supportive of learning and memory in experimental models. Evidence from human observational studies and intervention trials, however, is limited and variable, in study design, magnesium formulations, dosage regimen, and cognitive outcome measures. In addition, difficulty in evaluation of magnesium status makes the results of clinical assessments hard to interpret. In conclusion, the existing evidence highlights the significance of magnesium in brain health and cognition. The use of magnesium as a potentially beneficial nutritional factor for cognitive resilience is recommended but further well-designed randomized controlled trials are required to confirm its clinical efficacy, optimum supplementation protocols and long-term cognitive outcomes.