Gdue Plus a Hypocaloric Mediterranean Diet in Adults With MASLD

This was a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial conducted in adults with metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic syndrome, and moderate-to-severe hepatic steatosis.

Eligible participants were aged 18 years or older and had hepatic steatosis classified as grade S2 or S3 according to the controlled attenuation parameter (CAP), together with metabolic syndrome defined according to International Diabetes Federation criteria.

Participants were randomly assigned in a 1:1 ratio to one of two study groups:

Gdue® plus an individualized hypocaloric Mediterranean diet; or Matching placebo plus the same individualized hypocaloric Mediterranean diet.

Gdue® contained 237.5 mg of Ascophyllum nodosum, 12.5 mg of Fucus vesiculosus, and 7.5 µg of chromium picolinate per capsule. Participants took one capsule three times daily, approximately 30 minutes before the main meals, for 6 months. The placebo was provided in an indistinguishable dosage form and identical packaging to maintain masking.

All participants received individualized dietary counseling from a qualified dietitian. The dietary intervention consisted of a hypocaloric Mediterranean diet with an estimated energy deficit of approximately 600 to 1,000 kcal per day relative to individual energy requirements. The diet emphasized minimally processed foods, vegetables, fruit, whole grains, legumes, fish, nuts, and extra-virgin olive oil, while limiting refined sugars, sweetened beverages, processed foods, and excess saturated fat. Participants also received counseling on physical activity and were advised to avoid alcohol during the study.

Clinical and biochemical assessments were performed at baseline, approximately 3 months, and approximately 6 months. Evaluations included body weight, body mass index, waist circumference, blood pressure, fasting glucose, glycated hemoglobin, fasting insulin, HOMA-IR, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, liver enzymes, homocysteine, and serum creatinine.

Body composition was assessed at baseline and 6 months using bioelectrical impedance analysis. Liver steatosis was assessed using CAP, and liver fibrosis was evaluated using vibration-controlled transient elastography at baseline and 6 months.

Adherence to the study product was assessed by pill count and collection of unused capsules. Adherence to the Mediterranean diet was evaluated using the 14-item Mediterranean Diet Adherence Screener. Adverse events and treatment tolerability were recorded throughout the study.

IInclusion Criteria:

Age 18 years or older. Diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic syndrome according to International Diabetes Federation criteria, defined as central adiposity (waist circumference ≥94 cm in men and ≥80 cm in women) plus at least two of the following:

Triglycerides >150 mg/dL. HDL cholesterol <40 mg/dL in men or <50 mg/dL in women. Systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg, or ongoing antihypertensive treatment.

Fasting plasma glucose 110-125 mg/dL or established type 2 diabetes mellitus. Moderate-to-severe hepatic steatosis at baseline, defined as steatosis grade S2 or S3 according to Controlled Attenuation Parameter assessment.

Ability to understand the study procedures and provide written informed consent.

Exclusion criteria

Alcohol consumption >20 g/day in women or >30 g/day in men. Use of nutraceutical supplements within the previous 6 months. Use of anti-obesity pharmacological treatment within the previous 6 months. Renal insufficiency, defined as serum creatinine above the upper limit of the reference range.

Cancer. Chronic inflammatory diseases, including rheumatic or infectious disorders. Psychiatric disorders. Severe cardiovascular or cerebrovascular disease. New York Heart Association class II-IV heart failure. Prior myocardial infarction or stroke. Cerebrovascular event within the 6 months before enrollment.