Association of fish oil supplementation with risk of incident severe non-alcoholic fatty liver disease: a prospective study of 488 888 individuals.

Fish oil supplementation was associated with a 7% lower risk of incident severe NAFLD in a large prospective cohort.

• HR 0.93, 95% CI 0.87-0.99; P = 0.022
• Study included 488,888 UK Biobank participants
• Over 12.3 years of follow-up, 5,671 participants developed severe NAFLD
• Cox proportional hazards models were used to evaluate associations

C-reactive protein (CRP) partially mediated the association between fish oil supplementation and reduced severe NAFLD risk.

• CRP mediated 8.8% of the association between fish oil supplementation and severe NAFLD
• Mediation analysis was used to evaluate roles of serum metabolic and inflammatory biomarkers
• CRP was one of three biomarkers identified as partial mediators

High-density lipoprotein cholesterol (HDL-C) partially mediated the association between fish oil supplementation and reduced severe NAFLD risk.

• HDL-C mediated 7.5% of the association between fish oil supplementation and severe NAFLD
• HDL-C was identified alongside CRP and cystatin C as a partial mediator
• These findings suggest a lipid metabolism pathway through which n-3 PUFAs may affect NAFLD risk

Cystatin C partially mediated the association between fish oil supplementation and reduced severe NAFLD risk.

• Cystatin C mediated 10.0% of the association between fish oil supplementation and severe NAFLD
• Cystatin C had the largest mediation proportion among the three identified biomarkers
• Cystatin C is a marker of kidney function and has been linked to inflammatory and metabolic processes

No significant interactions were observed between fish oil supplementation and genetic variants linked to n-3 PUFA metabolism.

• Genetic interaction analyses included polymorphisms linked to n-3 PUFA metabolism
• All interaction P-values were >0.05
• The lack of gene-supplement interactions suggests the association may be broadly applicable regardless of genetic background related to n-3 PUFA metabolism