A randomized double-blind clinical trial investigating the effects of ellagic acid on glycemic status, liver enzymes, and oxidative stress in patients with non-alcoholic fatty liver disease.

2025-01-30
BMC complementary medicine and therapies 25(1)
- Sara Mighani
- Rasoul Samimi
- Mohamadreza Rashidi Nooshabadi
- Seyed Amir Farzam
- Hossein Khadem Haghighian
- Maryam Javadi

PubMed: 39885430
DOI: 10.1186/s12906-025-04759-4

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 44
Population: 44 patients with non-alcoholic fatty liver disease
Methods: randomized clinical trial, 180 mg of EA per day (n=22) or placebo (n=22) for 8 weeks
Duration: 8 weeks
Funding: Unclear

Background

It seems that oxidative stress is involved in the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). Considering the antioxidant features of Ellagic acid (EA), this study was designed to assess the effect of EA on some biochemical factors in patients with NAFLD.

Methods

In this clinical trial, 44 patients were selected based on including criteria and randomly received 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. At the beginning and end of the study, glycemic indices, lipid profiles, liver enzymes, oxidative stress markers, and inflammatory factors were measured.

Results

At the end of the study, the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05). Also, a significant increase in the mean of total antioxidant capacity (TAC) was observed in the EA group (P < 0.05). However, changes in high-density lipoprotein (HDL), total cholesterol (TC), and fasting blood sugar (FBS) were not significant in any of the groups (P > 0.05).

Conclusions

Based on the results, the present study provided evidence that EA can be used as a supplemental therapy alongside current treatment plans to reduce the complications of NAFLD due to its antioxidant and anti-inflammatory properties.

Trial registration

This study was prospectively registered at the Iranian Registry of Clinical Trials on the 23th of January 2022 (ID: IRCT20141025019669N21).

Research Insights

Raspberry→Improved Antioxidant Capacity
a significant increase in the mean of total antioxidant capacity (TAC) was observed in the EA group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Improved High-Density Lipoprotein Level
changes in high-density lipoprotein (HDL), total cholesterol (TC), and fasting blood sugar (FBS) were not significant in any of the groups (P > 0.05)
Effect
Neutral
Effect size
Small
Dose
180 mg per day
Raspberry→Improved Insulin Levels
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Improved Insulin Resistance
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Alanine Aminotransferase Level
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Alkaline Phosphatase Level
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Aspartate Aminotransferase Level
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Blood Cholesterol
changes in high-density lipoprotein (HDL), total cholesterol (TC), and fasting blood sugar (FBS) were not significant in any of the groups (P > 0.05)
Effect
Neutral
Effect size
Small
Dose
180 mg per day
Raspberry→Reduced C-Reactive Protein Levels
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Fasting Blood Glucose Levels
changes in high-density lipoprotein (HDL), total cholesterol (TC), and fasting blood sugar (FBS) were not significant in any of the groups (P > 0.05)
Effect
Neutral
Effect size
Small
Dose
180 mg per day
Raspberry→Reduced Gamma-Glutamyl Transferase Levels
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Low-Density Lipoprotein Level
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Malondialdehyde
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day
Raspberry→Reduced Triglyceride Levels
the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05)
Effect
Beneficial
Effect size
Moderate
Dose
180 mg per day