The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing in the U.S. as well as the rest of the world. It is the leading cause of abnormal liver enzymes and is associated with diabetes and obesity. Long term hyperglycemia causes an increase in the synthesis of fatty acids and triglycerides in the liver, leading to fatty liver.

At this time there are few guidelines for diagnostic and follow-up methods and limited proven treatment options. Previous research of pharmacological agents to treat NAFLD garnered poor results.

In a new study published this month in Phytotherapy Research, researchers investigated the effects of the bioflavonoid hesperidin on hepatic steatosis, liver enzymes, and inflammatory and metabolic biomarkers in patients with NALFD.

This randomized, double-blind, controlled clinical trial included 50 patients with NAFLD. Each patient supplemented with either 1 gram of hesperidin or placebo for 12 weeks. During the treatment, each group was advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, the patients in the hesperidin group demonstrated a significant reduction in alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), total cholesterol, triglyceride, hepatic steatosis, high-sensitivity C-reactive protein, tumor necrosis factor-α, and nuclear factor-κB (NF-κB).

As a result, this study demonstrates that hesperidin supplementation along with lifestyle modification is superior to lifestyle modification alone in managing NAFLD and improving lipid parameters. 

Insulin resistance, diabetes, obesity, and metabolic syndrome are all major key factors in the development of NAFLD, primarily driven by the excess intake of sugar. Previous research has demonstrated that patients with diabetes and metabolic syndrome often have vitamin C insufficiency due to increased metabolic and nutrient demands. Hesperidin is the most active bioflavonoid in citrus-based fruits such as oranges, lemons, and grapefruit, and facilitates the formation of vitamin C complex.

Other nutrients to consider with NAFLD include fish oil, tocotrienols, and probiotics. Numerous studies have demonstrated low polyunsaturated fat and the development of pathogenesis of NAFLD. In addition, supplementation with fish oil was associated with mitigating the disease process and improving lipid markers and insulin resistance in these patients. Fish oil supplementation restores insulin sensitivity and exerts anti-inflammatory actions. In addition, fish oil significantly reduces liver enzymes. Dosing ranges have been studied between 1 to 4 grams per day.

Tocotrienol supplementation has also been shown to help reduce liver enzymes as well as improve both inflammatory and oxidative stress markers in patients with NALFD. Dosing used has been 300 mg twice daily

Probiotics also play a role in improving NAFLD. They restore the gastrointestinal barrier function, modulate the immune system, and inhibit the proliferation of harmful bacteria. Probiotics have been shown to reduce liver fat and improve liver enzymes. Probiotics are likely most effective by preventing bacterial translocation and reducing the effects of the intestinal microbiota on the liver.

It is essential to encourage a restricted carbohydrate diet and exercise to support weight loss in these individuals. Combining dietary and lifestyle changes along with proper supplementation should be considered to help reduce the progression and improve liver function in patients with NAFLD.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Cheraghpour M, Imani H, et al. Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial. Phyother Res. 2019 Aug;33(8):2118-2125.