Article - Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review.

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Take home message

Polyphenol supplements show potential for the prevention and management of non-alcoholic fatty liver disease. However, current research has shown mixed results. Further clinical trials are needed to confirm these findings as well as provide optimal dose and duration.

Evidence category

B: Systematic reviews including RCTs of limited number

Summary review

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder estimated to affect 30.5% of people worldwide. There are currently no pharmacological interventions. The aim of this study was to critically assess evidence for the use of polyphenol supplementation for the prevention and management of NAFLD.

Methods

29 randomised controlled trials (RCTs) with a total population of 1840 participants aged 18-70 years, diagnosed with NAFLD were included in this systematic review.
Study durations ranged from 8-48 weeks. Intervention groups included between 10-69 patients.
11 phenolic compounds were examined: turmeric, curcumin, resveratrol, anthocyanins, naringenin, genistein, catechin, green tea extract, hesperidin, silybin and silymarin. These were taken orally in capsule form, either as single or combined compounds.
Measurement markers included: Liver enzymes (AST, ALP, ALT, GGT); Lipid profile (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)); Inflammation markers (TNF-alpha, CRP, IL-6, NAFLD score); Homeostasis Model Assessment-Insulin Resistance (HOMA-IR); and body mass index (BMI).
The method was conducted according to PRISMA guidelines.

Results

5/7 trials showed turmeric and curcumin significantly reduced ALT, AST and GGT.
7/14 trials showed significant improvements in TG, LDL-C, HDL-C, TC following supplementation with turmeric, curcumin, green tea extract, hesperidin and silymarin.
5/11 studies reported a significant reduction in TNF-@ levels after supplementation with curcumin, genistein, resveratrol and hesperidin.
Green tea extract and hesperidin reduced CRP in 3/7 studies.
Genistein significantly reduced IL_6 in 1 study.
5/7 studies reported NAFLD scores were significantly improved by curcumin, naringenin, silymarin and silybin.
Turmeric, curcumin, genistein, green tea extract, hesperidin, resveratrol and silybin improved HOMA-IR values in 9 trials.
In 9/16 trials BMI decreased following supplementation with turmeric, curcumin, genistein, green tea extract, hesperidin, naringenin and silymarin.

Conclusion

Supplementation with turmeric and curcumin may support the reduction of liver enzymes and inflammatory markers, and improve lipid profiles, insulin resistance and NAFLD scores in patients with NAFLD. The results for other polyphenols were inconsistent across studies.

Clinical practice applications

Obesity and insulin resistance are risk factors for NAFLD. A diet rich in polyphenols may help to decrease the inflammatory cascades and oxidative stress that are associated with these conditions.
A Mediterranean diet is naturally high in polyphenols; however, bioavailability varies greatly.
Supplements in liposomal and nanoparticle form can enhance absorption and availability.

Considerations for future research

Larger trials with longer durations and standardised interventions are needed to confirm the results.
Dose and duration of intervention need to be established.
Baseline differences between developing and developed countries may mean that the results may not be generalised to a global population.

Abstract

Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a challenging metabolic disorder with a strong emphasis on its prevention and management. Polyphenols, a group of naturally occurring plant compounds, have been associated with a decreased risk of various metabolic disorders related to NAFLD. The current systematic review aims to critically assess evidence about the ameliorative effect of polyphenol supplementation on NAFLD patients. A PRISMA systematic search appraisal was conducted in PubMed, Scopus, Web of Science Core Collection, and all relevant studies published prior to April 2024 and met the inclusion criteria were included. Twenty-nine randomized clinical trials (RCTs) comprised 1840 NAFLD patients. The studies primarily examined eleven phenolic compounds, including turmeric, curcumin, resveratrol, genistein, catechin, green tea extract, hesperidin, and silymarin. Turmeric and curcumin decreased liver enzymes, inflammatory cytokines, lipid profile, insulin resistance, and NAFLD score, while resveratrol did not present consistent results across all the studies. Most studies on silymarin showed a reduction in liver enzymes and lipid profile; however, no changes were observed in inflammatory cytokine levels. The dietary supplementation of hesperidin and naringenin or green tea extract caused improvements in liver enzyme, lipid profile, and inflammatory cytokine, while genistein supplementation did not modulate blood lipid profile. In conclusion, dietary supplementation of polyphenols could potentially prevent and ameliorate NAFLD. Still, the inconsistent results across the included RCTs require further clinical research to establish optimal dosage and duration.