The Effect of Magnesium Intake on Stroke Incidence: A Systematic Review and Meta-Analysis With Trial Sequential Analysis

Abstract

Background: The effect of magnesium on stroke has been consistently discussed less, and the results of previous studies have been contradictory. We reviewed the latest literature and quantified robust evidence of the association between magnesium intake and stroke risk. Methods: PubMed, EMBASE, the Cochrane Library, the Web of Science and ClinicalTrials.gov were searched through inception to January 15, 2019 for prospective cohort studies on magnesium intake and the incidence of stroke. Results: Fifteen studies with low bias involving 18 cohorts were entered into this study. The summary relative risk (RR) was significantly reduced by 11% for total stroke (RR: 0.89 [95% CI, 0.83-0.94]; P < 0.001) and by 12% for ischemic stroke (RR: 0.88 [95% CI, 0.81-0.95]; P = 0.001), comparing the highest magnesium intake category to the lowest. After adjusting for calcium intake, the inverse association still existed for total stroke (RR: 0.89 ([95% CI, 0.80-0.99]; P = 0.040). There was an inverse but non-significant association for hemorrhagic stroke, subarachnoid hemorrhage and intracerebral hemorrhage. The quantitative associations for total and ischemic stroke were robust. Importantly, high-risk females who had a body mass index (BMI) ≥25 kg/m² and who were subjected to a ≥12 y follow-up exhibited a greater decrease in RRs as a result of magnesium intake. For each 100 mg/day increase in magnesium, the risk for total stroke was reduced by 2% and the risk for ischemic stroke was reduced by 2%. Conclusions: Increasing magnesium intake may be a crucial component of stroke prevention that acts in a dose-dependent manner. However, the conclusion is limited by the observational nature of the studies examined, and further randomized controlled trials are still needed.

Keywords: magnesium; meta-analysis; stroke; systematic review; trial sequential analysis.

Figure 1

Forest plots of the risk of total stroke for magnesium intake (A) and for <50 mg/day (B), ≥50 and <100 mg/day (C), ≥100 and <150 mg/day (D), and ≥150 mg/day Magnesium Increments (E). A total of 15 publications including 18 cohorts: reporting data separately for males and females (9, 15, 16) within an article were treated as independent studies. RR, relative risk.

Figure 2

Trial Sequential Analysis (TSA) of total stroke comparing the highest magnesium intake category to the lowest. The TSA illustrated that the cumulative Z-curve crossed both the conventional boundary for benefit and the trial sequential monitoring boundary for benefit, demonstrating that the results are robust and conclusive, and further studies are not required. A diversity required information size (RIS) of 396,204 was computed by α = 0.05 (two-sided); 80% statistical power, with a conservative relative risk reduction of 5%. X-axis, the number of patients; Y-axis, cumulative Z-score; Dark red lines, conventional boundaries (upper for benefit, Z-score = 1.96; lower for harm, Z-score = −1.96; two-sided P = 0.05); Sloping red lines with black, filled circle icons, trial sequential monitoring boundaries (two sides, computed accordingly); Sloping blue line with black, filled circle icons, Z-curve; Vertical red full line, RIS computed accordingly; Upper conventional boundary for benefit, area of benefit; Lower conventional boundary for harm, area of harm; Middle area, futility area; Red lines with black, filled circle icons in the futility area, futility boundaries.

Figure 3

Trial sequential analysis of ischemic stroke comparing the highest magnesium intake category to the lowest.

Figure 4

Two-stage dose-response effects on the relationships between magnesium intake and total stroke (A); ischemic stroke (B); hemorrhagic stroke (C). The solid line represents non-linear estimates of the association between Magnesium Intake and the risk of expected outcomes; the dashed lines are the 95% confidence intervals (95% CIs); the dotted line represents the linear estimates of the associations between magnesium intake and the risk of expected outcomes. The vertical axis is the relative risk (RR) scale without logarithmic transformation.