Poor Magnesium Status Linked to Greater Mortality Risk in Patients with MASLD, MetALD

New research is shedding light on a significant association between global magnesium status and the risk of all-cause and cardiovascular disease (CVD) mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-associated liver disease (MetALD).1

Leveraging National Health and Nutrition Examination Survey (NHANES) data for more than 3000 US adults with MASLD or MetALD, the study found a higher magnesium depletion score (MDS) is longitudinally associated with increased risks of all-cause and CVD mortality, especially among those who do not meet the estimated average requirement of magnesium intake and those with a lower risk of advanced hepatic fibrosis.1

“To the best of our knowledge, this is the first study to establish a relationship between global magnesium status and all-cause and CVD mortality among individuals with MASLD or MetALD,” Lei Fan, MD, PhD, MPH, a fellow in the division of epidemiology at Vanderbilt University Medical Center, and colleagues wrote.1

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. Although resmetirom (Rezdiffra) became the first US Food and Drug Administration-approved MASH therapeutic in 2024, identifying patients at higher risk of mortality remains necessary for facilitating risk stratification and targeted intervention strategies.2,3

To examine the association between MDS and mortality in individuals with MASLD or MetALD, investigators assessed NHANES data for patients with ultrasound-confirmed hepatic steatosis with alcohol consumption < 20 g per day in women and 30 g per day in men and the presence of ≥ 1 of the following cardiometabolic criteria: overweight or obesity; diabetes; hypertension; plasma high-density lipoprotein cholesterol < 1.0 mmol/L for men and <1.3 mmol/L for women; or plasma triglycerides ≥ 1.70 mmol/L or under lipid-lowering treatment. Additionally, they assessed data for patients with ultrasound-confirmed hepatic steatosis and ≥ 1 of the cardiometabolic criteria, with alcohol consumption of 20–50 g per day in women or 30–60 g per day in men.1

In total, the study included 3802 patients, including 3560 with MASLD and 242 with MetALD. Their MDS was calculated by aggregating 4 factors influencing the reabsorption capability of the kidneys, including diuretic use; proton pump inhibitor use; kidney function; and alcohol consumption. ​​Higher MDS scores indicated more severe magnesium depletion. The primary outcomes included all-cause death, death from CVD, and death from cancer.1

In the combined MASLD and MetALD cohort, 1638 all-cause deaths occurred among 3802 participants over a median follow-up of 26 years, of which 542 were deaths from CVD and 360 were deaths from cancer. In the MASLD cohort, 1544 all-cause deaths occurred among 3560 MASLD participants over a median follow-up of 26 years, of which 517 died from CVD and 338 died from cancer.1

Upon analysis, in the combined cohort, MDS > 2 was associated with increased all-cause mortality (Hazard ratio [HR], 2.52; 95% CI, 1.77–3.61; P <.0001) and CVD mortality (HR, 3.01; 1.87–4.86; P <.0001) compared with MDS of 0.1

For all-cause mortality, investigators pointed out this association became stronger among participants who did not meet the estimated average requirement level of magnesium intake (HR, 2.72; 95% CI, 1.69–4.37; P = .001) and marginally attenuated among those who consumed magnesium above the estimated average requirement level (HR, 2.29; 95% CI, 1.36–3.85; P = .0003) (P-interaction = 0.93). Additionally, the association between MDS and all-cause mortality was stronger among those with FIB-4 < 1.3 (HR, 2.95; 95% CI, 1.69–5.15; P = .0006) and became weaker in those with FIB-4 ≥ 1.3 (HR, 1.89; 95% CI, 1.15–3.10; P = 0.04) (P-interaction = 0.57).1

For CVD mortality, the association became stronger among participants who did not meet the estimated average requirement level of magnesium intake (HR, 3.77; 95% CI, 1.88–7.55; P = .0004), whereas no significant association was observed among those who consumed magnesium above the estimated average requirement level (P = 0.93). The association was also stronger among those with FIB-4 < 1.3 (HR, 3.38; 95% CI, 1.77–6.44; P <.0001) but not in those with FIB-4 ≥ 1.3 (P = 0.32).1

“The MDS is a promising tool that needs to be investigated for risk stratification and disease management of patients with MASLD or MetALD, preferably among individuals at the early stages of MASLD,” investigators concluded.1 “Identifying MASLD/MetALD patients at high risk of Mg deficiency using the MDS, and correcting Mg deficiency through supplementation and dietary changes, may be important prevention strategies for reducing CVD mortality in MASLD/MetALD patients.”

References

1. Fan L, Zhu X, Zhang X, et al. Magnesium Depletion Score and Mortality in Individuals with Metabolic Dysfunction Associated Steatotic Liver Disease over a Median Follow-Up of 26 Years. Nutrients. https://doi.org/10.3390/nu17020244
2. AASLD. New MASLD Nomenclature. Accessed January 31, 2025. https://www.aasld.org/new-masld-nomenclature
3. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed January 31, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash