Magnesium Depletion and Cardiovascular Mortality: Unveiling the Connection in Hyperlipidemia

A new nationwide study suggests that magnesium depletion may be a significant and underrecognized risk factor for premature death in individuals with hyperlipidemia, a condition affecting more than one-third of U.S. adults. Researchers have introduced a novel clinical tool—the Magnesium Depletion Score (MgDS)—to help identify high-risk patients and potentially guide more personalized cardiovascular care.

Drawing from over 12,000 participants in the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, the study found that individuals with high MgDS had a significantly elevated risk of both all-cause and cardiovascular mortality, even after accounting for a wide range of demographic and clinical factors.

The MgDS, which integrates four common clinical variables—diuretic use, proton pump inhibitor use, impaired kidney function, and heavy alcohol intake—offers a practical alternative to cumbersome or unreliable methods of assessing magnesium status. Unlike serum magnesium levels, which often fail to detect chronic subclinical deficiency, the score was validated against the magnesium tolerance test, the current gold standard.

The researchers observed a clear dose-response relationship: each one-point increase in MgDS corresponded with an 18% higher risk of all-cause mortality and a 36% higher risk of cardiovascular death, independent of traditional risk factors like LDL cholesterol, blood pressure, and diabetes status.

Kaplan–Meier survival curves starkly illustrated the survival gap. Patients with high MgDS experienced the lowest probability of survival over the 20-year follow-up period, while those with low scores had the highest survival rates (log-rank p < 0.0001). Notably, even after adjusting for dietary magnesium intake, the mortality risk associated with MgDS remained significant, reinforcing the tool’s validity beyond nutritional intake alone.

Subgroup analyses highlighted certain populations where magnesium depletion may be particularly harmful. Among patients with prediabetes, elevated MgDS was strongly associated with cardiovascular mortality, suggesting metabolic dysregulation may intensify vulnerability. Similarly, current and former smokers with higher MgDS experienced greater mortality risk—likely due to tobacco’s role in impairing magnesium absorption and promoting LDL oxidation.

Heavy alcohol use also emerged as a potent modifier. Alcohol not only exacerbates lipid dysregulation but also depletes magnesium stores by increasing renal excretion. The study found that hyperlipidemic adults who drank heavily and had high MgDS were at notably higher risk of both cardiovascular and all-cause death.

Hyperlipidemia is a well-established driver of atherosclerotic cardiovascular disease (ASCVD), but current risk stratification tools rarely account for micronutrient status. The findings suggest MgDS could be integrated into clinical practice to improve identification of vulnerable patients—particularly those who may not otherwise be flagged using conventional risk calculators.

As an observational study, the research cannot establish causality, and it remains unclear whether correcting magnesium deficiency would directly reduce mortality. Moreover, MgDS includes variables—like diuretic use—that may reflect underlying disease severity rather than magnesium status alone.

This study adds to growing evidence that magnesium plays a crucial role in cardiovascular health—regulating vascular tone, preventing calcification, modulating oxidative stress, and supporting insulin sensitivity. Its deficiency may silently undermine conventional treatment efforts, particularly in patients with comorbidities like diabetes or chronic kidney disease.

As magnesium-rich diets and supplementation remain safe and inexpensive, clinicians may find that screening for and addressing depletion provides a cost-effective layer of risk management—especially in patients with persistent lipid abnormalities despite statin therapy.