Effect of Oral Calcium Butyrate Supplementation in Obesity

Overview

Obesity is characterized by gut microbiota dysbiosis, in which beneficial metabolites such as butyrate are reduced. Butyrate is a short-chain fatty acid produced by microbial fermentation that plays a key role in maintaining intestinal barrier integrity, regulating immune responses, and supporting mitochondrial function. Its depletion contributes to disruption of the intestinal barrier, facilitating the translocation of bacterial components and promoting systemic inflammation mediated by immune cell activation, like monocytes. This chronic inflammatory state is associated with mitochondrial dysfunction and impaired cellular bioenergetics. Butyrate has been investigated for its anti-inflammatory and metabolic effects, however, its direct impact on monocyte mitochondrial function and its relationship with gut microbiota composition in humans remains unclear. This randomized, double-blind, placebo-controlled trial will evaluate the effect of oral calcium butyrate supplementation (1000 mg/day) compared with placebo for 4 weeks in adults with obesity. The primary objective is to determine the change in monocyte mitochondrial maximal respiration baseline to week 4.

The study will consist of a screening phase (pre-admission) and two visits, followed by asynchronous follow-up. Pre-admission visit Participants meeting inclusion criteria (presence of obesity) will be recruited through advertisements published on official institutional platforms. Informed consent will be explained and signed prior to any study-related procedures. Participants will be informed about the study characteristics, procedures, risks, and expected benefits, including dietary intervention and biochemical assessments. A clinical history will be obtained, including identification data, contact information, medical history, and current or recent use of medications and supplements. Anthropometric measurements (weight and height) will be obtained for BMI calculation. Blood pressure will be measured after at least 5 minutes of rest, with two readings per arm separated by 3 minutes and averaged. A blood sample will be collected to determine glucose, creatinine, and liver function tests. Eligible participants will receive a stool collection kit with instructions for microbiota analysis and will be instructed to return the sample at the next visit. Visit 1: Baseline Anthropometric measurements will be recorded (weight, height, waist circumference). Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function. The stool sample collected will be received for microbiota and short-chain fatty acids analysis. Intervention Participants will be randomly assigned to either: Butyrate supplement group, or placebo group. An isocaloric maintenance diet will be prescribed (50% carbohydrates, 20% protein, 30% fat, 25 g/day fiber), including menus and food lists. Study capsules will be provided along with: Instructions for administration, adherence logbook, identification of adverse event monitoring (nausea, vomiting, abdominal discomfort, diarrhea, constipation, headache, dizziness, fatigue) Visit 2: Final (After 4 weeks of intervention) Nutritional and Clinical Assessment Anthropometric measurements will be recorded (weight, height, waist circumference). Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function and mitochondrial function. The stool sample collected will be received for microbiota and short-chain fatty acids analysis. Capsule count and adherence log review will be conducted. The adverse events questionnaire will be administered.