A Study to Evaluate the Effects of a Butyrate-Polyphenol Formulation on Gut Health and Associated Symptoms

NCT07371975 | Recruiting

• 1 other identifier: CL116
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy of a butyrate/polyphenol formulation on modulation of the gut microbiome and gastrointestinal symptoms using questionnaires in individuals with self-reported gastrointestinal discomfort.

Conditions

Gut Health

Keywords

Gastrointestinal discomfort; Abdominal pain; Gas; Bloating; Diarrhea; Constipation

Outcome Measures

Primary Outcomes (2)

• The Gastrointestinal Symptom Rating Scale (GSRS)-Irritable Bowel Syndrome (IBS) version

  Change in the Gastrointestinal Symptom Rating Scale-IBS from baseline. The responses to the questions range from no discomfort at all to very severe discomfort which would indicate a worse outcome

  14 days

• Gut Microbiome Stool Test

  Change in the Gut Microbiome (strain level, functional metrics, taxonomy abundance and composition) from baseline

  14 days

Secondary Outcomes (5)

• Digestion-Associated Quality of Life Questionnaire (DQLQ)

  14 days

• Visual Analogue Scale (VAS) of abdominal pain

  14 days

• Bristol Stool Form Scale (BSFS)

  14 days

• Gastrointestinal -Global Assessment of Improvement Scale (Gastrointestinal-GAI)

  14 days

• World Health Organization Quality of Life (WHOQOL-BREF)

  14 days

Study Arms (2)

Butyrate + Polyphenol Formulation

ACTIVE COMPARATOR

Butyrate + Polyphenol Formulation

Dietary Supplement: Butyrate + Polyphenol Formulation

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Butyrate + Polyphenol Formulation DIETARY_SUPPLEMENT

Butyrate + Polyphenol Formulation

Butyrate + Polyphenol Formulation

Placebo DIETARY_SUPPLEMENT

Placebo

Placebo

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 25-70 years
• Body mass index 18.5-34.9 kg/m2
• A GSRS-IBS score ≥ 21 (identification as having moderate or severe gastrointestinal symptoms). If the GSRS-IBS score is \< 20 (identification of minimal or mild), may be included at the discretion of the PI/Sub-I
• Experiencing at least three of the following conditions on a weekly basis (gastrointestinal discomfort, abdominal pain, gas, bloating, diarrhea, or constipation)
• Healthy based on medical history and without chronic disease (unless permitted in the judgment of the PI/Sub-I)
• Weight stable for the past six months (±6 lbs.)
• Willing and able to give written informed consent
• Ability to communicate and read in English
• Ability to comply with study requirements

You may not qualify if:

• Currently participating in another clinical research study
• Pregnant, planning pregnancy, or breastfeeding
• Unable to swallow capsules, tablets, or softgels
• Male participants and females of childbearing potential who are unwilling to use an acceptable method of contraception from screening through 30 days after study completion.
• Typically goes longer than 3 days without a bowel movement
• Current diagnosis of cardiovascular disease, history of an abnormal electrocardiogram (ECG), diabetes (Type 1 or Type 2), or cancer (except for non-melanoma skin cancer) within the past 5 years
• Having had a medical or surgical event in the past 5 years involving hospitalization, outpatient, or emergency care that requires ongoing monitoring.
• Planning to undergo a major medical procedure or surgical event within the next 30 days
• Currently being treated for any infectious disease
• Currently consuming more than 6 standard alcoholic drinks per week for women and 10 drinks per week for men (a standard alcoholic drink is defined as one bottle/can of beer, one glass of wine, or one ounce of hard liquor)
• Smoking or use of nicotine products daily within 30 days prior to screening
• Using substances of abuse or recreational drugs/substances, including tetrahydrocannabinol (THC), within the past 14 days
• History of intolerance or allergic reaction to product ingredients, including butyrate, tributyrin, polyphenols (Green tea extract, Grape Seed extract, Cinnamon extract, maltodextrin, silicon dioxide, magnesium stearate, or chlorophyllin)
• Having donated blood or received a blood/plasma transfusion within 30 days before baseline
• History of a major change in dietary habits within the past 1 month

Sponsors & Collaborators

• Supplement Formulators, Inc.: lead

Study Sites (1)

Life Extension Clinical Research, Inc.

Fort Lauderdale, Florida, 33304, United States

RECRUITING

Related Publications (19)

• Administration, D. o. H. a. H. S. U. S. F. a. D. (2005). Guidance for industry : estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers : pharmacology and toxicology. Center for Drug Evaluation and Research.

  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

• Conley BA, Egorin MJ, Tait N, Rosen DM, Sausville EA, Dover G, Fram RJ, Van Echo DA. Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. Clin Cancer Res. 1998 Mar;4(3):629-34.

  PMID: 9533530 BACKGROUND

• Cory H, Passarelli S, Szeto J, Tamez M, Mattei J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front Nutr. 2018 Sep 21;5:87. doi: 10.3389/fnut.2018.00087. eCollection 2018.

  PMID: 30298133 BACKGROUND

• Costa C, Tsatsakis A, Mamoulakis C, Teodoro M, Briguglio G, Caruso E, Tsoukalas D, Margina D, Dardiotis E, Kouretas D, Fenga C. Current evidence on the effect of dietary polyphenols intake on chronic diseases. Food Chem Toxicol. 2017 Dec;110:286-299. doi: 10.1016/j.fct.2017.10.023. Epub 2017 Oct 14.

  PMID: 29042289 BACKGROUND

• Cristofori F, Calabrese FM, Iacobellis I, Santamaria M, Celano G, Ferrocino I, Di Sabato E, Pergola R, Dargenio VN, Paulucci L, De Angelis M, Francavilla R. Calcium butyrate efficacy in pediatric irritable bowel syndrome: Randomized placebo-controlled multiomics-based clinical trial. J Pediatr Gastroenterol Nutr. 2025 Sep;81(3):551-561. doi: 10.1002/jpn3.70154. Epub 2025 Jul 9.

  PMID: 40635319 BACKGROUND

• Grosicki, G. (2021). Effects of 3-week Tributyrin Supplementation on the Gut Microbiome: A Pilot Study. Journal of the Academy of Nutrition and Dietetics, 121(9), A23.

  BACKGROUND

• Hodges, J. Z., M.; Cao, S.; Pokala, A.; Rezaei, S.; Sasaki, G.; Vodovotz, Y.; Bruno, R. (2022). Catechin-Rich Green Tea Extract Reduced Intestinal Inflammation and Fasting Glucose in Metabolic Syndrome and Healthy Adults: A Randomized, Controlled, Crossover Trial. Current Developments in Nutrition, 6, 981. https://doi.org/10.1093/cdn/nzac068.010

  BACKGROUND

• Hodgkinson K, El Abbar F, Dobranowski P, Manoogian J, Butcher J, Figeys D, Mack D, Stintzi A. Butyrate's role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr. 2023 Feb;42(2):61-75. doi: 10.1016/j.clnu.2022.10.024. Epub 2022 Nov 2.

  PMID: 36502573 BACKGROUND

• Huang Q, Braffett BH, Simmens SJ, Young HA, Ogden CL. Dietary Polyphenol Intake in US Adults and 10-Year Trends: 2007-2016. J Acad Nutr Diet. 2020 Nov;120(11):1821-1833. doi: 10.1016/j.jand.2020.06.016. Epub 2020 Aug 15.

  PMID: 32807722 BACKGROUND

• Kapolou, A. K. H. R., N; Koutelidakis, A. (2021). Association of Mean Daily Polyphenols Intake with Mediterranean Diet Adherence and Anthropometric Indices in Healthy Greek Adults: A Retrospective Study. Applied Sciences, 11(10). https://doi.org/10.3390/app11104664

  BACKGROUND

• Ljotsson B, Jones M, Talley NJ, Kjellstrom L, Agreus L, Andreasson A. Discriminant and convergent validity of the GSRS-IBS symptom severity measure for irritable bowel syndrome: A population study. United European Gastroenterol J. 2020 Apr;8(3):284-292. doi: 10.1177/2050640619900577. Epub 2020 Jan 14.

  PMID: 32213021 BACKGROUND

• Ma G., C., Y. (2020). Polyphenol supplementation benefits human health via gut microbiota: A systematic review via meta-analysis. . Journal of Functional Foods, 66(103829).

  BACKGROUND

• Park SY, Kim YD, Kim MS, Kim KT, Kim JY. Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial. Food Funct. 2023 Feb 6;14(3):1520-1529. doi: 10.1039/d2fo01835g.

  PMID: 36655542 BACKGROUND

• Pietrzak A, Banasiuk M, Szczepanik M, Borys-Iwanicka A, Pytrus T, Walkowiak J, Banaszkiewicz A. Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial. Nutrients. 2022 Aug 11;14(16):3283. doi: 10.3390/nu14163283.

  PMID: 36014789 BACKGROUND

• Qaisar R, Iqbal MS, Ahmad F, Karim A. Oral butyrate improves postural balance by repairing leaky gut in geriatric adults. Gait Posture. 2025 Sep;121:370-376. doi: 10.1016/j.gaitpost.2025.06.016. Epub 2025 Jun 24.

  PMID: 40577952 BACKGROUND

• Recharla N, Geesala R, Shi XZ. Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review. Nutrients. 2023 May 11;15(10):2275. doi: 10.3390/nu15102275.

  PMID: 37242159 BACKGROUND

• Rosner, B. (2006). Hypothesis Testing Two-Sample INference. In Fundamentals of Biostatistics (6th ed., pp. 331-334). Duxbury Press.

  BACKGROUND

• Wang X, Qi Y, Zheng H. Dietary Polyphenol, Gut Microbiota, and Health Benefits. Antioxidants (Basel). 2022 Jun 20;11(6):1212. doi: 10.3390/antiox11061212.

  PMID: 35740109 BACKGROUND

MeSH Terms

Conditions

Abdominal Pain; Mucopolysaccharidosis IV; Diarrhea; Constipation

Interventions

Butyrates

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Andrew Swick, PhD

  Life Extension

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven Hirsh

CONTACT

9542027679; shirsh@lifeextension.com

Barbara Martinez

CONTACT

9542842709; bmartinez@lifeextension.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: January 28, 2026
• Study Start: October 16, 2025
• Primary Completion: April 26, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)