Association between dietary magnesium intake, inflammation, and neurodegeneration

Abstract

Background: Consistent evidence shows that magnesium (Mg) intake is associated with lower blood pressure (BP), and that lower BP is associated with improved cerebral health. However, recent findings indicate that the positive effect of dietary Mg intake on cerebral health is not mediated by a decrease in BP. As Mg's anti-inflammatory action is a plausible alternative mechanism, the objective of this study was to investigate the associations between Mg intake and inflammation to determine whether it mediates any neuroprotective effect.

Methods: Participants from the UK Biobank (n = 5775, aged 40-73 years, 54.7% female) were assessed for dietary magnesium using an online food questionnaire, brain and white matter lesion (WML) volumes were segmented with FreeSurfer software, and inflammation markers including high-sensitivity C-reactive protein (hs-CRP), leukocyte, erythrocyte count, and Glycoprotein acetylation (GlycA) were measured using specific laboratory techniques such as immunoturbidimetry, automated cell counting, and nuclear magnetic resonance. Hierarchical linear regression models were performed to investigate the association between dietary Mg, and inflammatory markers and between dietary Mg, brain and WMLs volumes. Mediation analysis was performed to test a possible mediation role of inflammation on the association between dietary Mg and brain and WMLs volumes.

Results: Higher dietary Mg intake was associated with lower inflammation: hs-CRP level (- 0.0497%; 95% confidence interval [CI] - 0.0497%, - 0.0199%) leukocytes count (- 0.0015%; 95%CI - 0.00151%, - 0.0011%), and GlycA (- 0.0519%; 95%CI - 0.1298%, - 0.0129%). Moreover, higher dietary Mg intake was associated with larger grey matter volume (0.010%; 95%CI 0.004%, 0.017%), white matter volume (0.012%; 95%CI 0.003, 0.022) and right hippocampal volume (0.002%; 95%CI 0.0007, -0.0025%). Lower hs-CRP levels mediated the positive association between higher dietary Mg intake and larger grey matter volume.

Conclusions: The anti-inflammatory effects of dietary Mg intake in the general population, appears to mediate its neuroprotective effect.

Keywords: Brain volumes; Inflammation; Magnesium; UK biobank; White matter lesions.

Fig. 1

Mediation analysis testing whether the dietary magnesium (Mg) intake on grey matter volume (GM) is mediated through high-sensitivity c-reactive protein (hs-CRP). a = the effect of dietary Mg intake on hs-CRP, b = the effect of hs-CRP on the GM, c = the effect of dietary Mg intake on GM, c’= is the direct effect of dietary Mg intake on GM. The indirect effect was calculated with bootstrapping method (stimulation number = 1000)

Fig. 2

The figure illustrates the cellular mechanisms that connect higher levels of magnesium to a reduction in inflammatory response and improved cerebral health