GLUT-F Improves MASLD Liver Function

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.

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