MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)
Conditions
Keywords
Hepatic steatosis, Nutraceutical, Silybin, Glutathione, Vitamin E, Liver function
Brief summary
This randomized, double-blind, placebo-controlled, two-period crossover study evaluated the effects of GLUT-F, a nutraceutical formulation containing silibin-enriched silymarin, glutathione, and vitamin E delivered with Enterosoma® technology, in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). Participants received GLUT-F and placebo for 3 months each, separated by a 1-month washout period. The study assessed changes in hepatic steatosis, liver enzymes, metabolic parameters, inflammatory markers, and liver function measured by ultrasonography and the \^13C-methacetin breath test.
Detailed description
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is closely associated with obesity, insulin resistance, oxidative stress, and chronic low-grade inflammation. Although lifestyle modification remains the cornerstone of treatment, adherence is often poor and effective pharmacological therapies remain limited. GLUT-F is a nutraceutical formulation containing silibin-enriched silymarin, glutathione, and vitamin E encapsulated using Enterosoma® technology to improve the bioavailability of its active components. The combined antioxidant and hepatoprotective properties of these compounds may reduce hepatic steatosis and improve liver function in patients with MASLD. Objectives The primary objective was to evaluate the effect of GLUT-F supplementation on hepatic steatosis compared with placebo in adults with MASLD. Secondary objectives were to assess the effects of GLUT-F on liver metabolic function, liver enzymes, anthropometric measures, glucose metabolism, lipid profile, inflammatory biomarkers, and hepatic fibrosis. Methods This was a randomized, double-blind, placebo-controlled, two-period crossover clinical trial. Following a 2-week dietary run-in period, participants with ultrasonographically diagnosed MASLD were randomly assigned to receive either GLUT-F or matching placebo for 3 months. After a 1-month washout period, participants crossed over to receive the alternate treatment for an additional 3 months. Throughout the study, participants were instructed to maintain their habitual lifestyle and consume an isocaloric diet. Clinical assessments were performed at baseline and at the end of each treatment period. Liver steatosis was assessed by ultrasonographic steatosis grading and the hepatorenal index (HRI), while liver stiffness was evaluated by acoustic radiation force impulse (ARFI) elastography. Dynamic liver function was assessed using the ¹³C-methacetin breath test (¹³C-MBT), including cumulative percent dose recovery (cPDR) and delta over baseline (DOB). Additional assessments included anthropometric measurements, serum liver enzymes (ALT, AST, GGT), hepatic steatosis indices (HSI and FLI), fasting glucose, insulin, HOMA-IR, lipid profile, C-reactive protein, and a panel of inflammatory and metabolic mediators. The primary endpoint was the change in hepatic steatosis assessed by ultrasonography. Secondary endpoints included changes in liver function, liver enzymes, metabolic and inflammatory biomarkers, and safety. Treatment effects were analyzed using linear mixed-effects models accounting for treatment, period, sequence, and baseline values, with participants included as random effects.
Interventions
DIETARY_SUPPLEMENTGLUTatios FOrte
GLUT-F is an oral nutraceutical formulation containing silibin-enriched silymarin, reduced glutathione, and vitamin E encapsulated using Enterosoma® technology to enhance intestinal absorption and bioavailability. Participants received one sachet daily for 3 months. The placebo was identical in appearance, taste, and packaging but contained no active ingredients.
DIETARY_SUPPLEMENTPlacebo
The placebo consisted of an oral formulation identical to GLUT-F in appearance, taste, packaging, and mode of administration, but containing no active ingredients. It was administered as one sachet daily for 3 months to maintain participant and investigator blinding.
Sponsors
University of Bari
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, double-blind, placebo-controlled, two-period crossover study. Participants were randomly assigned to receive either GLUT-F followed by placebo or placebo followed by GLUT-F, with each intervention lasting 3 months and separated by a 1-month washout period. Each participant served as their own control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Evidence of hepatic steatosis (≥ grade 1) at screening. * Body mass index (BMI) ≥25 kg/m² or presence of metabolic dysfunction consistent with MASLD diagnostic criteria. * Stable body weight (no significant weight change during the 3 months preceding enrollment). * Willingness to maintain usual dietary habits, physical activity, and concomitant medications throughout the study. * Ability to provide written informed consent.
Exclusion criteria
* Excessive alcohol consumption (\>30 g/day for men or \>20 g/day for women). Other known causes of chronic liver disease, including viral hepatitis (HBV or HCV), autoimmune liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, or drug-induced liver disease. * Evidence of liver cirrhosis, hepatic decompensation, hepatocellular carcinoma, or other severe liver disorders. * Previous bariatric surgery or planned bariatric surgery during the study period. * Current use of medications or nutritional supplements known to significantly affect hepatic steatosis or liver function unless on a stable dose for at least 3 months before enrollment. * Pregnancy or breastfeeding. * Severe renal, cardiovascular, respiratory, endocrine, or malignant disease that could interfere with study participation. * Known allergy or hypersensitivity to silybin, glutathione, vitamin E, or any component of the study product. * Any condition that, in the investigator's judgment, could compromise participant safety or adherence to the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver steatosis grade | At baseline and at the end of intervention (3 months) | Change in liver steatosis grade from baseline to the end of each treatment period, assessed by abdominal ultrasonography using a standardized semiquantitative steatosis grading system and the hepatorenal index (HRI), which quantifies hepatic echogenicity relative to the renal cortex. Lower steatosis grade and HRI values indicate improvement in hepatic fat accumulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver function | At baseline and after the end of intervention (3 months) | Change from baseline to the end of each treatment period in liver metabolic function assessed by the ¹³C-methacetin breath test. Functional parameters included cumulative percent dose recovery (cPDR), reflecting hepatic microsomal metabolic capacity, and delta over baseline (DOB), reflecting hepatic substrate extraction and metabolism. Higher cPDR and normalization of abnormal cPDR or DOB values indicate improved liver function. |
| Change in Liver Enzyme Levels | At baseline and after the intervention (3 months) | To evaluate the change in liver enzyme levels from baseline to the end of the treatment period. Liver function will be assessed by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT). Results will be reported as mean change from baseline and compared between treatment groups. |
Countries
Italy
Outcome results
None listed