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

Abstract

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 to draw conclusions on the effects of Mg supplements. Cohort studies showed inconsistent dose-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 ∼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 mmol/L) [<0.75 compared with 0.85 mmol/L: pooled hazard ratio (HR) = 1.43; 95% confidence 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).

Keywords: Alzheimer’s disease; adults; cognition; cognitive impairment; dementia; dietary magnesium; magnesium supplement; meta-analysis; serum magnesium; systematic review.

FIGURE 1

PRISMA flow diagram showing the process of literature search and study selection.

FIGURE 2

Results of cohort studies examining the associations of dietary Mg (A) and circulating Mg (B) with cognitive disorders. AD, Alzheimer's disease; ARIC, Atherosclerosis Risk in Communities study; CGPS, Copenhagen General Population Study; MCI, mild cognitive impairment; Mg, magnesium; NA, not available; REGARDS, Reasons for Geographic and Racial Differences in Stroke Study; WHIMS, Women’s Health Initiative Memory Study.

FIGURE 3

Re-analysis of the associations between Mg exposures and all-cause dementia based on predefined cutoffs for Mg. Given that the EAR for Mg varies with sex and age, we adopted 308 mg/d as the cutoff in the analysis, which is the average of the EARs for males (350 mg/d) and females (265 mg/d) aged over 30 y. All studies reported HRs for all-cause dementia as outcome, except for Chen et al. [53] reporting ORs for cognitive impairment defined by SIS score ≤4 and Tu et al. [56] reporting ORs for cognitive impairment 1 mo after stroke defined by MMSE score. CI, confidence interval; df, degree of freedom; EAR: Estimated Average Requirement; HR, hazard ratio; Mg, magnesium; MMSE, Mini-Mental State Examination; OR, odds ratio; RE, random-effects; REF, reference group; SIS, 6-Item Screener.