Eur J Clin Nutr. , 2020., Jul 9. doi: 10.1038/s41430-020-0679-3.

The Efficacy of Flaxseed and Hesperidin on Non-Alcoholic Fatty Liver Disease: An Open-Labeled Randomized Controlled Trial

Yari Z Cheraghpour M Alavian SM et al.

Abstract

Background/objectives: Non-alcoholic fatty liver disease (NAFLD) is growing in prevalence globally and no definitive evidence for any approved pharmacological approaches for patients with NAFLD has been found yet. This study was aimed to assess the clinical effects of flaxseed and hesperidin in patients with NAFLD. Subjects/methods: In this randomized, controlled, clinical trial, one hundred eligible patients with NAFLD were enrolled and randomly assigned to four dietary intervention groups including lifestyle modification program (control), lifestyle modification program with 30 g whole flaxseed powder, lifestyle modification program with 1 g hesperidin supplementation, and lifestyle modification program with combination of 30 g flaxseed and 1 g hesperidin (flax-hes) for 12 weeks. The changes in anthropometric parameters, metabolic profiles of glucose and lipids, inflammatory biomarkers and hepatic steatosis and fibrosis were evaluated.  Results: After the 12-week dietary interventions, significant reductions in body mass index, glucose hemostasis parameters and hepatic steatosis were observed in all groups. Repeated measures analysis of variance revealed a significant effect for time relative to almost all paraclinical parameters. Post hoc analysis with Bonferroni correction revealed that the three intervention groups experienced significant decreases in plasma levels of alanine aminotransferase, indices of insulin resistance and insulin sensitivity, fasting glucose and fatty liver index compared to control (p < 0.008). Conclusions: In conclusion, our study confirmed that hesperidin and flaxseed supplementation improved glucose and lipid metabolism, while reduced inflammation and hepatic steatosis (controlled attenuation parameter) in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.

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Key Points

Flaxseed, due to its nutritional components, can be considered as a promising adjunct intervention for reducing the risk of weight-related metabolic abnormalities such as dyslipidemia, insulin resistance, cardiovascular risk factors and it is a good choice for weight loss.  Hesperidin is an antioxidant flavonoid found in high concentrations in citrus. Together, flaxseed, because of the high content of omega-3 and fiber and its other components, and hesperidin, due to its potent antioxidant activity can be an effective combination in managing NAFLD. A randomized, controlled, open-label clinical trial to investigate the efficacy of flax-hes supplementation in patients with NAFLD was conducted. In the present study, amelioration of dyslipidemia in response to supplementation with hesperidin and/or flaxseed was achieved. No differences were seen in control group, while in the other three groups, plasma levels of TG, TC, and LDL-C decreased significantly during 12 weeks. HDL-C levels also increased significantly in the flaxseed group. CAP score, as an indicator of hepatic steatosis, reduced considerably in all intervention groups, while no significant differences were detected among four groups. These findings indicate the significant effects of lifestyle modification on hepatic steatosis, which diluted the effects of supplements on liver steatosis. Only flaxseed supplementation could ameliorate the hepatic fibrosis.

In conclusion, the study confirmed that hesperidin and flaxseed supplementation, alone or in combination together, improved glucose and lipid metabolism, while reduced some inflammatory factors and CAP score in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.