Modulating the Progression: Combined Effects of Magnesium Supplementation and Intermittent Fasting on Tau Hyperphosphorylation in Alzheimer’s Disease

Alzheimer's disease (AD) is a neurodegenerative condition, often associated with aging and genetic hereditary, where profound modifiable risk factors are still being studied. AD is a progressive neurodegenerative disorder, with tau protein hyperphosphorylation playing a central role in its pathogenesis. Phosphatases (enzymes that remove phosphate groups from proteins) can counteract tau hyperphosphorylation, potentially slowing disease progression. Magnesium has been shown to activate phosphatases and reduce oxidative stress, suggesting it may help regulate tau phosphorylation. Similarly, intermittent fasting (IF) has been found to significantly increase Brain-Derived Neurotrophic Factor (BDNF) in animals, which may further enhance phosphatase activity, particularly protein phosphatase 2A (PP2A), involved in tau dephosphorylation. A randomized controlled trial will assign participants to one of four groups: a control group, an IF-only group, a magnesium-only group, and a combined magnesium + IF group. Primary outcomes might include changes in hyperphosphorylated tau levels, measured by ELISA in cerebrospinal fluid (CSF), and glucose variability, assessed via continuous glucose monitors (CGMs). This study aims to explore the combined effects of magnesium supplementation and IF on tau phosphorylation in individuals with early-stage AD. We hypothesize that it is likely both magnesium and IF, particularly in combination, will result in reduced tau phosphorylation and improved metabolic health. Previous studies of magnesium and IF corresponding to AD have been conducted on mice, but the exact correlation of these interventions in humans, their relation to phosphatase activity in TP, and how they complement each other are still yet to be investigated. This research could provide insights into dietary interventions as potential strategies for slowing AD progression.