Effect of Oral Calcium Butyrate Supplementation in Obesity

NCT07583017 | Not Yet Recruiting DMC

• 1 other identifier: FNU-5904-26-27-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Keywords

Obesity; Butyrate; Gut microbiota; mitochondria; monocyte; short chain fatty acid

Outcome Measures

Primary Outcomes (2)

• Monocyte mitochondrial maximal respiration in pmol O₂/min/10⁶

  Change in maximal respiration measured in Cluster of differentiation 14 (CD14+) monocytes using extracellular flux mitochondrial stress testing. Maximal respiration will be calculated as peak oxygen consumption rate (OCR) after Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) stimulation minus non-mitochondrial respiration, and compared between the intervention and placebo groups.

  From baseline to week 4 of the intervention

• Gut microbiota composition as relative abundance percentage

  Changes in gut microbiota composition will be assessed by 16 svedberg unit (16S) ribonucleic acid ribosomal (rRNA) sequencing, including alpha diversity (Chao1, Shannon), beta diversity, and relative taxonomic. and compared between the intervention and placebo groups.

  From baseline to week 4 of the intervention

Secondary Outcomes (3)

• Monocyte mitochondrial reserve respiratory capacity in pmol O₂/min/10⁶ cells

  From baseline to week 4 of the intervention

• Monocyte Bioenergetic Health Index (BHI) score

  From baseline to week 4 of the intervention

• Fecal butyrate concentration in µmol/g

  From baseline to 4 week of the intervention

Other Outcomes (15)

• Body mass index in kg/m²

  From baseline to 4 week of the intervention

• Skeletal muscle mass percentage

  From baseline to 4 week of the intervention

• Waist circumference in centimeter

  From baseline to 4 week of the intervention

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will receive oral placebo capsules containing maltodextrin at a dose of 600 mg/day, administered as two 300 mg capsules once daily for 4 weeks. Furthermore, the participants will follow the same standardized isocaloric maintenance diet (50% carbohydrates, 20% protein, 30% fat) throughout the study.

Dietary Supplement: Placebo

Butyrate

EXPERIMENTAL

Participants will receive calcium butyrate capsules at a dose of 1000 mg/day (2 capsules of 500 mg) by oral administration once daily for 4 weeks. Furthermore, the participants will follow the same standardized isocaloric maintenance diet (50% carbohydrates, 20% protein, 30% fat) throughout the study.

Dietary Supplement: Calcium butyrate

Interventions

Placebo DIETARY_SUPPLEMENT

Oral placebo capsules containing maltodextrin, 300 mg per capsule. Participants assigned to the placebo comparator arm will take two capsules once daily, for a total dose of 600 mg/day, for 4 weeks.

Placebo

Calcium butyrate DIETARY_SUPPLEMENT

Oral calcium butyrate capsules, 500 mg per capsule. Participants assigned to the experimental arm will take two capsules once daily, for a total dose of 1000 mg/day, for 4 weeks.

Butyrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signing of the informed consent form.
• Adults aged ≥18 years of age.
• Body mass index (BMI) \>30 kg/m².
• Both sex

You may not qualify if:

• Diabetes mellitus, defined as fasting glucose \>126 mg/dL during screening.
• Hypertension, defined as blood pressure ≥130/80 mmHg during screening.
• Chronic kidney disease or estimated glomerular filtration rate \<60 mL/min/1.73 m².
• Known liver disease.
• Secondary causes of obesity or diabetes, including Cushing syndrome, clinical or subclinical hypothyroidism, or pheochromocytoma.
• Catabolic diseases such as cancer or acquired immunodeficiency syndrome.
• Drug treatment:
• Antihypertensive drugs or treatment (thiacycline, loop or potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, alpha blockers, calcium antagonists, beta blockers).
• Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or insulin and antidiabetic drugs.
• Treatment with statins, fibrates or other drugs to control dyslipidemia.
• Use of antibiotics in the three months prior to the study.
• Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
• Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
• Supplements with any of the functional foods used in the study.
• Probiotic, prebiotic or symbiotic supplements.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico City, 14080, Mexico

Location

Related Publications (8)

• Borja-Magno AI, Furuzawa-Carballeda J, Guevara-Cruz M, Arias C, Granados J, Bourges H, Tovar AR, Sears B, Noriega LG, Gomez FE. Supplementation with EPA and DHA omega-3 fatty acids improves peripheral immune cell mitochondrial dysfunction and inflammation in subjects with obesity. J Nutr Biochem. 2023 Oct;120:109415. doi: 10.1016/j.jnutbio.2023.109415. Epub 2023 Jul 10.

  PMID: 37437746 BACKGROUND

• Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clin Nutr. 2024 Aug;43(8):1914-1928. doi: 10.1016/j.clnu.2024.06.036. Epub 2024 Jul 5.

  PMID: 39003957 BACKGROUND

• Marino F, Petrella L, Cimmino F, Pizzella A, Monda A, Allocca S, Rotondo R, D'Angelo M, Musco N, Iommelli P, Catapano A, Bagnato C, Paolini B, Cavaliere G. From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System. Biomolecules. 2025 Apr 29;15(5):638. doi: 10.3390/biom15050638.

  PMID: 40427531 BACKGROUND

• Guo Y, Shao M, Guan P, Yu M, Geng L, Gao Y, Meng L, Qu B. Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins. Plants (Basel). 2024 Jun 30;13(13):1807. doi: 10.3390/plants13131807.

  PMID: 38999647 BACKGROUND

• Kalkan AE, BinMowyna MN, Raposo A, Ahmad MF, Ahmed F, Otayf AY, Carrascosa C, Saraiva A, Karav S. Beyond the Gut: Unveiling Butyrate's Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review. Nutrients. 2025 Apr 9;17(8):1305. doi: 10.3390/nu17081305.

  PMID: 40284169 BACKGROUND

• Coppola S, Avagliano C, Calignano A, Berni Canani R. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021 Jan 28;26(3):682. doi: 10.3390/molecules26030682.

  PMID: 33525625 BACKGROUND

• Cleophas MCP, Ratter JM, Bekkering S, Quintin J, Schraa K, Stroes ES, Netea MG, Joosten LAB. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci Rep. 2019 Jan 28;9(1):775. doi: 10.1038/s41598-018-37246-7.

  PMID: 30692581 BACKGROUND

• Coppola S, Nocerino R, Paparo L, Bedogni G, Calignano A, Di Scala C, de Giovanni di Santa Severina AF, De Filippis F, Ercolini D, Berni Canani R. Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2244912. doi: 10.1001/jamanetworkopen.2022.44912.

  PMID: 36469320 BACKGROUND

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Martha Guevara, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY DIRECTOR

Central Study Contacts

Martha Guevara, MD, PhD

CONTACT

+52 55 5487 0900; martha.guevarac@incmnsz.mx

Lilia Noriega, PhD

CONTACT

+52 55 5487 0900; lilia.noriegal@incmnsz.mx

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research

Study Record Dates

• First Submitted: April 29, 2026
• First Posted: May 13, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)