Association between serum methylmalonic acid and metabolic dysfunction-associated steatotic liver disease:...

Area of Science:

• Metabolic health and liver disease research
• Biomarker analysis in chronic conditions
• Nutritional epidemiology

Background:

• Methylmalonic acid (MMA) is recognized as a marker of mitochondrial dysfunction.
• Mitochondrial dysfunction is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD).
• The specific role of MMA in MASLD pathogenesis requires further elucidation.

Purpose of the Study:

• To investigate the association between MMA levels and the risk of MASLD.
• To evaluate the potential mediating role of the Dietary Inflammatory Index (DII) in this association.
• To explore population heterogeneity in the MMA-MASLD relationship.

Main Methods:

• Analysis of data from 6959 participants in the National Health and Nutrition Examination Survey (1999-2014).
• Application of multivariate logistic regression and mediation analysis.
• Stratified and interaction analyses to assess population heterogeneity and independence from dietary factors.

Main Results:

• A statistically significant inverse dose-response relationship was observed between higher MMA levels and a lower risk of MASLD (P-trend = .048).
• The association between MMA and MASLD risk was largely independent of the DII and dietary inflammation.
• Subgroup analyses indicated the protective association was more pronounced in males, normal-weight individuals, and those younger than 60 years.

Conclusions:

• MMA may exert a protective effect against MASLD, contrary to its role solely as a marker of mitochondrial dysfunction.
• The observed protective association is population-specific and independent of dietary inflammation.
• Further research with longitudinal designs and direct steatosis assessment is warranted to confirm these findings.