Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis

Magnesium (Mg) plays a key role in neurological functioning and manifestations. However, the evidence from randomized controlled trials (RCTs) and cohorts on Mg and cognitive health among adults has not been systematically reviewed. We aimed to examine the associations of various Mg forms (supplements, dietary intake, and biomarkers) with cognitive outcomes by summarizing evidence from RCTs and cohorts. PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for relevant peer-reviewed articles published up to May 3, 2024. Three random-effects models were performed, when appropriate, to evaluate the relationship between Mg and cognitive outcomes: 1) linear meta-regression, 2) nonlinear (quadratic) meta-regression, and 3) meta-analysis using Mg variables categorized based on pre-existing recommendations. Three RCTs and 12 cohort studies were included in this systematic review. Evidence from the limited number of RCTs was insufficient fi cient to draw conclusions on the effects of Mg supplements. Cohort studies showed inconsistent dose-response - response relationships between dietary Mg and cognitive disorders, with high heterogeneity across populations. However, consistent U-shape associations of serum Mg with all-cause dementia and cognitive impairment were found in cohorts, suggesting an optimal serum Mg concentration of similar to 0.85 mmol/L. This nonlinear association was detected in meta-regression (P-quadratic = 0.003) and in meta-analysis based on the reference interval of serum Mg (0.75-0.95 - 0.95 mmol/L) [<0.75 < 0.75 compared with 0.85 mmol/L: pooled hazard ratio (HR) = 1.43; 95% confidence fi dence interval (CI) = 1.05, 1.93; > 0.95 compared with 0.85 mmol/L: pooled HR = 1.30; 95% CI = 1.03, 1.64]. More evidence from RCTs and cohorts is warranted. Future cohort studies should evaluate various Mg biomarkers and collect repeated measurements of Mg intake over time, considering different sources (diet or supplements) and factors affecting absorption (for example, calcium-to-Mg intake ratio). This systematic review was preregistered in PROSPERO (CRD42023423663).