Associations of serum n–3 and n–6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have suggested that dietary fat quality is associated with the development of NAFLD. OBJECTIVES: Our purpose was to investigate the cross-sectional and longitudinal associations of serum n–3 (ω-3) and n–6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD. METHODS: After exclusions, the cross-sectional analyses included 1533 men examined in 1984–1989 and 674 men and 870 women examined in 1998–2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991–1993 and 301 men and 466 women examined in 2005–2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI >60. ANCOVA and logistic regression were used for analyses. RESULTS: In the longitudinal analyses, participants with higher serum concentrations of total n–6 PUFA and linoleic acid, the major n–6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n–3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD. CONCLUSIONS: In middle-aged and older Finnish adults, higher serum concentrations of total n–6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.