Clinical Trials Using HepatoKeeper Herbal Essentials to Treat Non-alcoholic Fatty Liver Disease and Metabolic Factors
Condition: Non-alcoholic Fatty Liver Disease; Liver Fibrosis; Liver Injury
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis
Study type: Interventional

Summary: 
      Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with an
      estimated prevalence of approximately 15 to 30%. The incidence of NAFLD is even higher,
      reaching up to 58%, in individuals who are overweight or obese. The pathogenesis of NAFLD is
      complex and not fully understood. The metabolism of carbohydrates contributes to the
      development of NAFLD, as it increases the enzymatic activity of lipid synthesis in the liver,
      depleting adenosine triphosphate (ATP) rapidly and causing stress on mitochondria and
      endoplasmic reticulum. The multifunctional protein Glycine N-methyltransferase (GNMT) plays a
      regulatory role in liver carbohydrate metabolism, and its expression is downregulated in the
      liver tissues of NAFLD.

      While weight loss and lifestyle adjustments are helpful in controlling NAFLD, effective
      pharmacological or healthcare interventions for NAFLD patients are currently lacking. Insulin
      resistance is crucial in the pathogenesis of NAFLD, suggesting that drugs improving insulin
      sensitivity, such as metformin, might have therapeutic effects. However, recent large-scale
      clinical trial results have not supported this hypothesis. We propose that the mitochondrial
      inhibitory effects of metformin may be related to this discrepancy, and the negative effects
      may be reversed through food containing substances promoting GNMT gene expression, such as
      Ganwei (as know as "HepatoKeeper"). Preliminary animal experiments also show that the
      combined use of metformin and GNMT enhancers effectively eliminates liver lipid droplet
      accumulation and improves liver inflammation in a NAFLD mouse model, surpassing the effects
      of either drug used alone.

      Based on these findings, our team designed the medication treatment group for this clinical
      trial, aiming to investigate whether the combination of Ganwei and metformin produces a
      synergistic effect in humans. Ganwei compound herbal extract capsules contain extracts from
      natural foods such as Schisandra chinensis, Paeonia lactiflora, and Punica granatum. Among
      them, Paeonia lactiflora is known to contain components that enhance GNMT expression. Animal
      and cell experiments have demonstrated its potential for repairing liver damage and
      inflammation. This trial aims to assess the impact of orally administering Ganwei compound
      herbal extract capsules on participants and evaluate its effects on fatty liver, liver
      fibrosis, and metabolic indicators.
    

Detailed description: 
      Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with an
      estimated prevalence of approximately 15 to 30%. The incidence of NAFLD is even higher,
      reaching up to 58%, in individuals who are overweight or obese (Schwenger, 2014). With the
      Westernization of diets and insufficient physical activity, the prevalence of obesity,
      diabetes, and hyperlipidemia has been increasing in Taiwan in recent years, contributing to
      the gradual rise in the prevalence of NAFLD. NAFLD is strongly associated with metabolic
      syndrome, cardiovascular diseases, insulin resistance, and may progress to hepatitis, liver
      fibrosis, and even cirrhosis (Fazel, 2016; Amr, 2020).

      The pathogenesis of NAFLD is complex and not fully understood. Current understanding suggests
      that environmental factors such as diet, exercise, obesity, gut microbiota, and genetics play
      a role in the development of NAFLD. The liver, responsible for metabolizing major substances
      including carbohydrates and fatty acids, becomes overwhelmed, leading to the production of
      toxic lipids. Disruptions in lipid metabolism, inhibition of mitochondrial function, and
      impaired export of triglycerides from liver cells contribute to the accumulation of lipids
      within the liver. Insulin resistance further exacerbates this process. Additionally, lipid
      alterations in liver cells increase oxidative stress and activate cell signaling, triggering
      immune responses that damage liver cells and contribute to the development of fatty liver
      inflammation, fibrosis, and potentially liver cancer (Fazel, 2016; Amr, 2020).

      The metabolism of carbohydrates also contributes to NAFLD, as it increases the enzymatic
      activity of lipid synthesis in the liver, depleting adenosine triphosphate (ATP) rapidly and
      causing stress on mitochondria and endoplasmic reticulum. This results in liver cell
      necrosis, contributing to the development of NAFLD. The multifunctional protein Glycine
      N-methyltransferase (GNMT) plays a regulatory role in liver carbohydrate metabolism, and its
      expression is downregulated in the liver tissues of NAFLD (Liao, 2012).

      While weight loss and lifestyle adjustments are helpful in controlling NAFLD, effective
      pharmacological or healthcare interventions for NAFLD patients are currently lacking (Julien
      et al., 2019; Mary et al., 2020). Insulin resistance is crucial in the pathogenesis of NAFLD,
      suggesting that drugs improving insulin sensitivity, such as metformin, might have
      therapeutic effects. However, recent large-scale clinical trial results have not supported
      this hypothesis. We propose that the mitochondrial inhibitory effects of metformin may be
      related to this discrepancy, and the negative effects may be reversed through food containing
      substances promoting GNMT gene expression, such as Ganwei (as know as "HepatoKeeper").
      Preliminary animal experiments also show that the combined use of metformin and GNMT
      enhancers effectively eliminates liver lipid droplet accumulation and improves liver
      inflammation in a NAFLD mouse model, surpassing the effects of either drug used alone.

      Based on these findings, our team designed the medication treatment group for this clinical
      trial, aiming to investigate whether the combination of Ganwei and metformin produces a
      synergistic effect in humans. Ganwei compound herbal extract capsules contain extracts from
      natural foods such as Schisandra chinensis, Paeonia lactiflora, and Punica granatum. Among
      them, Paeonia lactiflora is known to contain components that enhance GNMT expression (Kyu-Han
      et al., 2020; Rajni et al., 2019). Animal and cell experiments have demonstrated its
      potential for repairing liver damage and inflammation. This trial aims to assess the impact
      of orally administering Ganwei compound herbal extract capsules on participants and evaluate
      its effects on fatty liver, liver fibrosis, and metabolic indicators.
    

Intervention name(s): Ganwei; Metformin; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Capsules; Tablets; Matching capsules
Other intervention name(s): HepatoKeeper; A10BA02
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Ganwei; Non-alcoholic fatty liver disease; metformin