Effects of Oral Sodium Butyrate Supplementation on Body Weight Reduction in Overweight/Obese Individuals With and Without Type 2 Diabetes (ButRed)

The goal of this clinical trial (randomized controlled trial with parallel group design) is to evaluate the effects of oral sodium butyrate supplementation for 12 weeks, compared with placebo, in addition to a moderately hypocaloric diet, on body weight, body composition, glucose metabolism, and lipid metabolism in overweight or obese individuals with and without type 2 diabetes.

The main questions this study aims to answer are:

• Does oral sodium butyrate improve body weight reduction and body composition compared with placebo?
• Does it improve glucose and lipid metabolism in participants with and without type 2 diabetes?

The study includes 46 men and women aged 30-70 years, with overweight or obesity (BMI 25-39.9 kg/m²) and HbA1c ≤ 7.0%. Participants are randomly assigned to receive either oral sodium butyrate or placebo, both combined with a moderately hypocaloric diet for 12 weeks.

Participants:

• Take sodium butyrate tablets (625 mg three times daily; total 1,875 mg/day) or placebo tablets with meals
• Follow a personalized, balanced hypocaloric diet monitored by a dietitian
• Attend clinic visits every two weeks for anthropometric measurements and dietary adherence checks
• Complete a 7-day food diary and a gastrointestinal symptom questionnaire (PAGI-SYM)
• Undergo fasting blood tests, body composition analysis (bioelectrical impedance), and continuous glucose monitoring (CGM) at baseline and after 12 weeks

Study Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: Sodium Butyrate (NaBut); Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Federico II University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women with overweight or obesity (Body Mass Index [BMI] between 25.0 and 39.9 kg/m²), with or without type 2 diabetes Age between 30 and 70 years HbA1c ≤ 7.5%

Exclusion Criteria:

• Cardiovascular events (myocardial infarction and/or stroke) within the previous 6 months
• Renal insufficiency (serum creatinine > 1.5 mg/dL) or hepatic impairment (ALT or AST levels more than twice the upper limit of normal)
• Anemia (hemoglobin < 12 g/dL)
• Insulin therapy or use of antihyperglycemic drugs other than metformin
• Use of antibiotics, probiotics, or prebiotics within the previous 3 months
• Habitual intense physical activity
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Sodium Butyrate Supplementation (NaBut); Participants receive oral sodium butyrate (NaBut) in combination with a moderately hypocaloric diet. Sodium butyrate is administered in tablet form (Butir Bioma®, UNIFARCO S.p.A.), with each tablet containing 625 mg of sodium butyrate. Participants take one tablet three times daily-at breakfast, lunch, and dinner-for a total daily dose of 1,875 mg.	Dietary supplement: Sodium Butyrate (NaBut); Participants receive oral sodium butyrate (NaBut) in combination with a moderately hypocaloric diet for 12 weeks. Sodium butyrate is administered as 625 mg tablets (Butir Bioma®, UNIFARCO S.p.A.), taken three times daily with meals (breakfast, lunch, and dinner), for a total daily dose of 1,875 mg. The hypocaloric diet is individualized based on basal metabolic rate (measured by indirect calorimetry) and physical activity level, with a 300-500 kcal/day energy reduction.
Placebo Comparator: Placebo; Participants receive placebo tablets in combination with the same moderately hypocaloric diet as the experimental group (NaBut arm). The placebo tablets are identical in appearance, weight, shape, color, and taste to the sodium butyrate tablets but do not contain the active ingredient (sodium butyrate). Participants take one placebo tablet three times daily-at breakfast, lunch, and dinner-for a total of three tablets per day.	Dietary supplement: Placebo; Participants receive placebo tablets identical in appearance, weight, shape, color, smell, and taste to the sodium butyrate tablets but without the active ingredient, combined with the same moderately hypocaloric diet as the experimental group. Tablets are taken three times daily with meals (breakfast, lunch, and dinner), for a total of three tablets per day. The hypocaloric diet follows the same composition and energy restriction as described for the sodium butyrate intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Body Weight After 12 Weeks of Oral Sodium Butyrate Supplementation Compared With Placebo	Body weight is measured at baseline and after 12 weeks of treatment. The primary outcome is the reduction in body weight (kg) from baseline to week 12 between the sodium butyrate and placebo groups.	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Composition (Fat Mass, Lean Mass, and Fat-Free Mass)	Body composition is assessed by bioelectrical impedance analysis (BIA) at baseline and after 12 weeks to evaluate changes in fat mass, lean mass, and fat-free mass between groups.	baseline and 12 weeks
Changes in Continuous Glucose Monitoring (CGM) Parameters	Continuous glucose monitoring (CGM) is performed for 7 days at baseline and at the end of treatment to evaluate mean glucose levels, variability, and time-in-range between groups.	baseline and 12 weeks
Changes in Fasting Glucose	Fasting plasma glucose is assessed at baseline and at week 12 by immunoenzymatic assay; results are reported in mg/dl	Baseline and 12 weeks
Changes in fasting insulin	Fasting plasma insulin is assessed at baseline and at week 12 by ELISA method and expressed in µU/ml	Baseline and 12 weeks
Changes in glycated hemoglobin (HbA1c)	Glycated hemoglobin (HbA1c) was measured at baseline and after 12 weeks in fasting whole-blood samples by high-performance liquid chromatography (HPLC) and was expressed as mmol/mol and %.	Baseline and 12 weeks
Changes in serum lipids	Fasting serum triglycerides, total cholesterol and HDL cholesterol are evaluated at baseline and after 12 weeks using immunoenzymatic methods and all expressed in mg/dL	Baseline and 12 weeks
Changes in Short-Chain Fatty Acids (SCFA)	Serum concentrations of short-chain fatty acids (acetate, propionate, butyrate) are measured at baseline and after 12 weeks. SCFA levels are assessed as metabolic markers of gut microbial activity and host metabolic response to sodium butyrate supplementation. They were quantified by gas chromatography with flame ionization detection (GC/FID) and expressed in μmol/L	Baseline and 12 weeks
Changes in Intestinal Permeability Markers_Zonulin	Fasting serum zonulin, as a biomarker of intestinal permeability, is measured at baseline and after 12 weeks by ELISA and expressed in ng/mL	Baseline and 12 weeks
Changes in Intestinal Permeability Markers_LPS	Fasting serum lipopolysaccharide (LPS), a biomarker of intestinal permeability, is measured at baseline and after 12 weeks by ELISA and expressed in pg/mL	Baseline and 12 weeks
Changes in Inflammatory Markers_hsCRP	Serum high-sensitivity C-reactive protein (hs-CRP) concentrations are measured at baseline and after 12 weeks using immunoturbidimetric methods and expressed in mg/dL	Baseline and 12 weeks
Changes in Gut Microbiota Composition	Fecal samples are collected at baseline and after 12 weeks to evaluate the effects of sodium butyrate on gut microbiota composition, compared to placebo. Microbial community structure is analyzed using 16S rRNA gene sequencing and shotgun metagenomic techniques to assess taxonomic and functional changes	baseline and 12 weeks
Changes in Inflammatory Markers_TNFalfa_IL-6	Serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations are measured at baseline and after 12 weeks using ELISA and are expressed in pg/mL	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: Lutgarda Bozzetto, Full Professor, Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2024
• Primary Completion (Actual): August 8, 2025
• Study Completion (Actual): August 8, 2025

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: obesity; lipid metabolism; type 2 diabetes; glucose control; body weight; Butyrate; butyrate supplementation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Body Weight; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Butyrates; Butyric Acid
• Other Study ID Numbers: 44/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no secure institutional infrastructure is currently available to support anonymized data sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No