Consumption of freshwater fish was associated with greater improvement in liver fat content and other metabolic phenotypes in patients with nonalcoholic fatty liver disease (NAFLD), according to a study in the American Journal of Gastroenterology.
The randomized, open-label, controlled clinical trial included patients aged 18 to 70 years, who were clinically diagnosed with NAFLD with hepatic steatosis 10% or greater, estimated by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).
The participants were randomly assigned 1:1 to a freshwater fish-based diet (F group) or the combination of a freshwater fish-based diet and a red meat-based diet with a daily alternating frequency (F/M group).
For the F group, freshwater fish (alternation of bighead carp and grass carp on a daily basis) was the only source of animal protein and fat in the usual diet. In the F/M group, a combination of freshwater fish (bighead and grass carp) and red meat (beef, pork, and mutton) with a daily alternation (1 cycle of this alternate diet is a 2-day period) was the only source of animal protein and fat in the usual diet.
Study visits occurred at baseline and at day 84 of the intervention. The visits included medical history, anthropometric evaluation, and fasting blood collection, and fecal samples. The change in liver fat content as measured by MRI-PDFF in the F group compared with the change in the F/M group at 84 days was the primary clinical outcome.
The F group had significantly greater consumption of freshwater fish without red meat, poultry, eggs, and dairy products compared with baseline, and the F/M group had a significantly higher intake of red meat and freshwater fish without poultry, eggs, and dairy products during the intervention.
At day 84 in the F group, a significant decrease in liver fat content was observed compared with day 0 (P <.01). Also, a decrease in liver fat content at day 84 was observed in the F/M group, although no significant difference occurred (P >.05). At the end of the intervention, the F group had a greater absolute decrease in hepatic steatosis vs the F/M group (-4.89% vs -1.83%, respectively, P =.032). The relative decrease in liver fat content was also significantly greater in the F group (-28.08%) compared with the F/M group (-10.57%, P =.041) during the intervention.
The levels of alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), ferritin, and waist circumference (WC) improved significantly in the F group at day 84. The level of WC was significantly reduced in the F/M group. In addition, the improvement in ALT, GGT, TG, HDL-c, FBG, IL-6, and ferritin was significantly greater in the F group vs the F/M group.
At day 84 in the F group, Faecalibacterium was enriched in fecal samples and negatively correlated with liver fat content and ALT, TG, and IL-6. Also, Escherichia-Shigella, Prevotella 9, and Megamonas were reduced at day 84 in the F group.
Total short-chain fatty acid (SCFA), propionic acid (PA), butyric acid (BA), and valeric acid (VA) levels were increased significantly (P <.01) at day 84 in the F group, and AA was significantly increased (P <.01) in the F/M group. In addition, the levels of unconjugated BAs significantly increased and the levels of conjugated BAs significantly decreased in the F group. A decreasing trend was found for conjugated BAs, and the levels of other BAs were stable throughout in the F/M group.
Limitations include the small sample size and short study duration. Also, liver biopsies were not used to determine changes in liver inflammation and fibrosis, and the study was not double-blinded. Furthermore, the freshwater fish intervention resulted in a significant improvement in hepatic steatosis, but it was not decreased to the normal range.
“The freshwater fish-based diet induces a greater improvement in hepatic steatosis and other metabolic phenotypes by regulating gut microbiota and its metabolites compared with the alternating freshwater fish-based and red meat-based diet, independent of weight change,” the study authors wrote. “In addition, the alternating freshwater fish and red meat consumption may not exacerbate NAFLD, more appropriate to fit the daily eating habits and food diversity for long-term implementation.”
He K, Guo L-L, Tang H, et al. A freshwater fish-based diet alleviates liver steatosis by modulating gut microbiota and metabolites: a clinical randomized controlled trial in Chinese participants with nonalcoholic fatty liver disease. Am J Gastroenterol. 2022;117(10):1621-1631. doi:10.14309/ajg.0000000000001885