Abstract
PURPOSE: Previous studies have shown that high-dose supplementation with n-3 polyunsaturated fatty acids (PUFAs) may benefit patients with nonalcoholic fatty liver disease (NAFLD), but the association of n-3 PUFAs with NAFLD among individuals with normal diets is only speculative. We investigated the cross-sectional and prospective associations between n-3 PUFAs and NAFLD in Chinese adults. METHODS: This community-based prospective study included 3049 men and women (40-75 years) in Guangzhou, China, whose participants completed an NAFLD ultrasound evaluation and erythrocyte PUFA tests. A total of 2660 participants underwent the second NAFLD evaluation approximately 3 years later. α-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. RESULTS: After adjusting for potential confounders, we observed inverse associations between DHA, DHA + EPA, total n-3 PUFAs and the presence of NAFLD in the cross-sectional analysis. The adjusted odds ratios (95% confidence interval) of NAFLD for the highest (vs. lowest) tertile were 0.74 (0.61, 0.90) for DHA, 0.82 (0.67, 1.00) for EPA, 0.73 (0.60, 0.88) for DHA + EPA and 0.74 (0.61, 0.91) for total n-3 PUFAs (all P values≤0.05). Over the average 3.12 years of follow-up, higher levels of DHA was associated with an improvement of NAFLD. The hazard ratio of improved NAFLD for the highest tertile was 1.18 (95% CI 1.09, 1.33) for DHA. Pathway analyses showed that favorable associations may be mediated by improvements in inflammatory markers (e.g., interleukin 1 beta and tumor necrosis factor alpha-like). CONCLUSIONS: Erythrocyte membrane n-3 PUFAs are inversely associated with the presence and progression of NAFLD in Chinese adults.
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Key Points
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid infiltration in hepatocytes and covers a wide spectrum of disease states, from benign hepatocellular steatosis and nonalcoholic steatohepatitis (NASH) to liver cirrhosis and end-stage liver disease (e.g., cancer). Here, a prospective cohort study was conducted to test the hypothesis that higher levels of erythrocyte membrane n-3 PUFAs are correlated with a lower NAFLD risk in middle-aged and elderly individuals in a Chinese population. The study demonstrated that erythrocyte membrane n-3 PUFAs (DHA, EPA, but not
ALA) were favorably associated with the presence and progression of NAFLD. Due to the difficulty in dietary assessments and the limitation in a food composition database for assessing fatty acids using an FFQ or dietary record method, the greater accuracy and precision of erythrocyte membrane n-3 PUFAs would improve the validity of association between n-3 PUFAs (in particular ALA) and NAFLD. There are limitations to the study. First it did not re-measure the erythrocyte membrane n-3 PUFAs levels during the follow-up visits. The changes in n-3 PUFA levels in erythrocytes with time may attenuate the favorable association that was observed. Next, the NAFLD status was evaluated using ultrasonography, but this method is not the gold standard (e.g., liver biopsy, CT or MRI) and may increase misclassification error. Finally, it was difficult to exclude potential residual confounding covariables. Although a prospective study provided a clear time relationship, the study could not finalize the causality as has been done by RCTs.