Silymarin-alpha lipoic acid and metabolic dysfunction-associated steatotic liver disease: Insights and methodological considerations

Table 1 Key methodological considerations for future nutraceutical trials in metabolic dysfunction-associated steatotic liver disease

Domain	Recommendation
Trial arms	Include three arms: SM-ALA + diet, SM-ALA only, and diet only
Primary outcomes	Use validated non-invasive endpoints (e.g., MRI-PDFF, ELF score)
Sample size	Perform power analysis; consider adaptive designs with interim analyses
Adherence monitoring	Combine self-report with biomarkers (e.g., plasma carotenoids), apps, third-party
Regulatory considerations	Include early-phase PK/PD and safety data (phase I) before efficacy claims
Mechanistic support	Provide preclinical or translational evidence on SM-ALA’s pathways
Reporting transparency	Follow CONSORT and report manufacturer involvement and conflicts of interest

SM-ALA: Silybum marianum and alpha-lipoic acid; PK: Pharmacokinetics; PD: Pharmacodynamics; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction; ELF: Enhanced liver fibrosis; CONSORT: Consolidated Standards of Reporting Trials.