Naringenin supplementation may reduce the severity of fatty liver and improve blood lipids Original paper

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term for a broad spectrum of liver disorders that affect people who are not heavy alcohol users and is characterized by excess deposition of triglycerides in liver cells. Currently, there are no approved medical therapies for NAFLD treatment, which has spurred interest in the potential use of different nutrients and supplements. Naringenin is a natural citrus-derived flavanone that has demonstrated various favorable effects in experimental models, including reductions in blood lipids.^[1] Could it be a useful option for people with NAFLD?

In this 4-week randomized controlled trial, 44 patients (average age of 46) with NAFLD and overweight or obesity were assigned to receive 200 milligrams per day of naringenin or a placebo. All participants were advised to maintain their normal diet and physical activity during the intervention.

The primary outcomes were NAFLD grade, as measured by ultrasonography, and the NAFLD fibrosis score (NFS). The secondary outcomes were body weight, alanine aminotransferase (ALT, a marker of liver function), aspartate aminotransferase (AST, a marker of liver function), and lipid profile.

Compared to placebo, naringenin reduced NAFLD grade as well as body weight (mean difference: −1.5 kg), triglycerides (mean difference: −78.4 mg/dL), total cholesterol (mean difference: −24.9 mg/dL), and LDL-C (mean difference: −13.3 mg/dL) and increased HDL-C (mean difference: +3.3 mg/dL). However, there were no differences between groups in AST, ALT, and NFS.

Ultrasonography was used to measure the severity of fatty liver, a method that is inferior to liver biopsy for detecting mild fatty liver. Consequently, some cases may have been missed in this study. Additionally, the outcomes listed in the preregistered paper are at odds with the published version. Specifically, AST, insulin resistance index, C-reactive protein, adiponectin, and neuregulin-4 were initially listed as the primary outcomes, and NAFLD grades and NFS were not included. The authors also did not adjust for multiple comparisons, despite the inclusion of multiple outcomes, which increases the risk of false-positive results. These issues reduce our confidence in the findings.