Mediterranean diet and associated metabolite signatures in relation to MASLD progression: A prospective cohort study
Kai Wang1,2, Shijian Xiang3, Qiangsheng He1,2
1Department of Epidemiology and Biostatistics, Clinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
Background:
Mediterranean diet (MED) is recommended for managing metabolic dysfunction-associated steatotic liver disease (MASLD). However, associations between MED adherence, related metabolite signatures, and risks of liver-related events (LRE) and mortality in MASLD patients remain unclear.
Methods:
We performed a prospective analysis using UK Biobank data, including 47,429 MASLD participants free of LRE at baseline. MED adherence was assessed as alternate Mediterranean Diet (aMED) score through a validated questionnaire. Metabolic biomarkers were measured using high-throughput nucleic magnetic resonance (NMR) spectroscopy. Cox regression and restricted cubic splines assessed the association of aMED, its components, with risk of LRE and mortality. Mediation analysis evaluated the role of metabolites in the relationship between aMED, its components, and MASLD progression.
Results:
Over a median follow-up of 13.3 years, 296 LRE cases and 3616 deaths occurred. Higher aMED scores (6-9) were associated with lower risks of LRE (HR: 0.553, 95% CI: 0.351-0.874) and mortality (HR: 0.854, 95% CI: 0.762-0.956) compared with the lowest scores (0-3), with linear dose-response relationships. Vegetables and legumes were associated with lower LRE risk, while vegetables, nuts, fish, MUFA:SFA ratio, and moderate alcohol intake were linked to reduced mortality. Of 143 metabolites, 46 were significantly associated with aMED. Omega-3 fatty acids, the omega-3 to total fatty acid ratio, and albumin accounted for 7.9%, 11.9%, and 2.6% of the reduction in LRE, and 19.4%, 23.1%, and 4.7% of the mitigation in mortality, respectively.
Conclusions:
Adherence to MED is linked to reduced LRE risk and mortality in MASLD patients. Metabolic biomarkers, particularly small HDL particles and omega-3 fatty acids, may mitigate MASLD progression.
Insights
Adhering to the Mediterranean diet (MED) significantly lowers liver-related event (LRE) and mortality risks in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Key metabolites like omega-3 fatty acids and albumin mediate these protective effects.
Area of Science:
- Hepatology
- Nutritional Science
- Metabolomics
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) management often involves the Mediterranean diet (MED).
- The specific impact of MED adherence and its metabolite signatures on liver-related events (LRE) and mortality in MASLD patients requires further clarification.
Purpose of the Study:
- To investigate the association between Mediterranean diet (MED) adherence, metabolite profiles, and the risk of liver-related events (LRE) and mortality in individuals with MASLD.
- To explore the mediating role of specific metabolites in the protective effects of the MED against MASLD progression.
Main Methods:
- Prospective analysis of UK Biobank data from 47,429 MASLD participants without baseline LRE.
- Assessment of Mediterranean diet (MED) adherence using the alternate Mediterranean Diet (aMED) score and measurement of metabolic biomarkers via NMR spectroscopy.
- Application of Cox regression, restricted cubic splines, and mediation analysis to determine associations and mediating pathways.
Main Results:
- Higher aMED scores correlated with significantly reduced risks of LRE and all-cause mortality, demonstrating a dose-response relationship.
- Specific dietary components like vegetables, legumes, nuts, fish, and moderate alcohol intake were associated with lower LRE and mortality risks.
- Metabolites including omega-3 fatty acids, omega-3 to total fatty acid ratio, and albumin were identified as significant mediators in the protective effects of the MED.
Conclusions:
- Adherence to the Mediterranean diet (MED) is associated with a substantial reduction in liver-related events (LRE) and mortality among MASLD patients.
- Metabolic biomarkers, particularly omega-3 fatty acids and small HDL particles, play a crucial role in mitigating MASLD progression and associated risks.
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