Butyrate and Polyphenols for Gut Health

Overseen By Andrew Swick, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Supplement Formulators, Inc.

Must not be taking: Proton pump inhibitors, Antibiotics

Disqualifiers: Gastrointestinal disease, Cancer, Diabetes, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to assess their impact on gut health and related symptoms. Participants will receive either a butyrate formulation (a type of short-chain fatty acid), a combination of butyrate and polyphenols, or a placebo. The study focuses on how these treatments affect gut health and permeability (the ease with which substances pass through the gut lining). It suits individuals who generally feel healthy but experience frequent gut issues, such as bloating or discomfort, several times a week. Participants must be comfortable fasting overnight and able to complete study tasks on two separate days. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on gut health improvements.

Do I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've taken proton pump inhibitors or oral antibiotics in the past 3 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that butyrate is generally safe for people. In one study, 66 adults with irritable bowel syndrome (IBS) who took sodium butyrate daily reported less stomach pain. This suggests that butyrate might help with gut problems without causing major side effects. However, sodium butyrate can harm the eyes, so it should be handled with care.

For the combination of butyrate and polyphenols, less direct safety information is available. Polyphenols, natural compounds found in plants, have been shown to improve gut health and support the gut lining, suggesting they are usually safe and beneficial for the gut.

While these findings are encouraging, more research is needed to fully understand the safety of these combinations. Consulting a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce unique approaches to improving gut health. Unlike typical treatments that might focus on dietary changes or probiotics, these formulations utilize butyrate and polyphenols, which are compounds known for their anti-inflammatory properties and ability to support the gut lining. The butyrate formulation directly delivers this short-chain fatty acid, which is naturally produced by beneficial gut bacteria, while the butyrate + polyphenol formulation combines this with polyphenols, compounds found in fruits and vegetables that further enhance gut health by promoting beneficial bacterial growth. These innovative approaches aim to directly target gut inflammation and enhance gut microbiome balance, potentially offering a more holistic and effective solution than traditional options.

What evidence suggests that this trial's treatments could be effective for gut health?

Research has shown that butyrate can improve gut health by promoting intestinal growth, boosting the immune system, and reducing inflammation. It also balances gut bacteria and strengthens the gut lining. Polyphenols, found in foods like berries and tea, support gut health by encouraging the growth of beneficial bacteria. In this trial, participants will receive either a Butyrate Formulation or a Butyrate + Polyphenol Formulation. When combined, butyrate and polyphenols have effectively treated conditions like colitis and colorectal cancer. Together, they enhance the gut environment and may offer significant health benefits. ^{3 6 7 8 9}

Who Is on the Research Team?

Andrew Swick, Ph.D

Principal Investigator

Life Extension

Are You a Good Fit for This Trial?

This trial is for individuals experiencing gut health issues. Participants should be interested in testing the effects of two different supplement formulations on their gut health and related symptoms.

Inclusion Criteria

I am generally healthy based on my medical history.

Willing to follow study instructions, including compliance with the study procedures and requirements

BMI of 18.5-34.9

Exclusion Criteria

I have used hormone-based birth control recently or plan to change it during the study.

I have had issues with my digestive system, like IBD or gallstones.

Currently on a galactose/lactose restricted diet

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a Butyrate formulation, a Butyrate + Polyphenol formulation, or a placebo daily for 28 days

4 weeks

Remote video calls scheduled during the study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Butyrate Formulation
• Butyrate + Polyphenol Formulation

Trial Overview The study is examining how effective a Butyrate formulation alone, or combined with Polyphenols, is compared to a placebo in improving gut health and reducing permeability issues.

How Is the Trial Designed?

Group I: Butyrate Formulation Active Control 1 Intervention

Butyrate Formulation: Take daily in the morning with 8 oz. (240ml) of water

Group II: Butyrate + Polyphenol Formulation Active Control 1 Intervention

Butyrate + Polyphenol Formulation: Take daily in the morning with 8 oz. (240ml) of water

Group III: Placebo Placebo Group 1 Intervention

Placebo: Take daily in the morning with 8 oz. (240ml) of water

Butyrate Formulation is already approved in European Union, United States for the following indications:

Approved in European Union as Sodium butyrate for:

• Gastrointestinal disorders
• Inflammatory bowel disease

Approved in United States as Sodium butyrate for:

• Gastrointestinal disorders
• Inflammatory bowel disease

Who Is Running the Clinical Trial?

Supplement Formulators, Inc.

Lead Sponsor

Trials

14

Recruited

570+

Compound Solutions Inc.

Collaborator

Trials

5

Recruited

250+

Compound Solutions Inc.

Industry Sponsor

Trials

5

Recruited

250+

Published Research Related to This Trial

Sodium butyrate (NaB) effectively reduces the proliferation, invasion, and metastasis of colorectal cancer (CRC) cells in a dose- and time-dependent manner, promoting apoptosis and causing a G1 phase cell cycle block.

The study identified 666 differentially expressed mRNAs and 30 lncRNAs linked to NaB's effects on CRC, with specific mRNAs like HMGA2, LOXL2, and ST7 showing significant correlations with patient prognosis, highlighting NaB's potential as a therapeutic agent through complex molecular mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network. Xi, Y., Jing, Z., Wei, W., et al.[2023]

Monoesters of polyol fatty acid esters (sefsols) significantly enhance the permeation of diclofenac through rat skin, with propylene glycol monocaprylate showing the highest enhancement in in vitro studies.

In vivo experiments demonstrated that adding 10% propylene glycol monocaprylate to diclofenac sodium suspension greatly increased plasma concentrations of diclofenac, indicating its potential as an effective transdermal absorption enhancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of polyol fatty acid esters on diclofenac permeation through rat skin. Takahashi, K., Matsumoto, T., Kimura, T., et al.[2019]

In a long-term study of 793 subjects with knee osteoarthritis, the topical solution of diclofenac sodium (TDiclo) demonstrated a safety profile similar to shorter trials, with the most common adverse effects being mild skin reactions at the application site, such as dry skin and contact dermatitis.

No significant increase in serious adverse events or risks of cardiovascular or cataract issues were observed, indicating that TDiclo can be safely used for up to 52 weeks in treating knee pain associated with osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee. Shainhouse, JZ., Grierson, LM., Naseer, Z.[2013]

Na-butyrate enema significantly improved symptoms of TNBS-induced colitis in rats, showing similar effectiveness to the standard treatment, SASP, in reducing colonic injury and inflammation.

The study found that Na-butyrate not only helped in healing the colonic mucosa but also increased the mitotic index, indicating enhanced cell proliferation compared to SASP, suggesting a potential mechanism for its therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Investigation of the effect of Na-butyrate on TNBS induced rat colitis]. Hu, R., Ouyang, Q., Wang, H.[2013]

In a pilot study involving 49 patients with inflammatory bowel diseases (IBD), sodium-butyrate supplementation for 2 months significantly altered the gut microbiota, promoting the growth of beneficial bacteria that produce short-chain fatty acids (SCFAs), which have anti-inflammatory properties.

Patients with ulcerative colitis experienced an improvement in quality of life after treatment with sodium-butyrate, suggesting potential clinical benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. Facchin, S., Vitulo, N., Calgaro, M., et al.[2021]

Polyvinyl butyrate nanoparticles (PVBu NPs) of different sizes (100 nm and 200 nm) were developed for controlled release of butyrate, showing significant suppression of inflammatory responses in macrophages, with 200 nm NPs being more effective in ameliorating colitis.

Interestingly, the 200 nm NPs combined with all-trans retinoic acid (ATRA) demonstrated enhanced therapeutic effects despite ATRA alone typically worsening inflammation, suggesting a potential synergistic approach for treating inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis. Li, J., Mu, Y., Liu, Y., et al.[2021]

Sodium butyrate (NaB) significantly reduces the severity of ulcerative colitis in a mouse model, improving survival rates and various health indicators such as colon length and disease activity index.

NaB works by inhibiting oxidative stress and inflammation through the activation of the COX-2/Nrf2/HO-1 pathway, while also promoting mitophagy, which helps protect cells from damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Butyrate Inhibits Oxidative Stress and NF-κB/NLRP3 Activation in Dextran Sulfate Sodium Salt-Induced Colitis in Mice with Involvement of the Nrf2 Signaling Pathway and Mitophagy. Bian, Z., Zhang, Q., Qin, Y., et al.[2023]

A new liquid suppository system using poloxamers and sodium chloride was developed for diclofenac sodium, which is stable and easy to administer without leakage, showing promise as a rectal dosage form.

The formulation demonstrated effective retention in the rectum for at least 6 hours in animal studies, indicating its potential for improved therapeutic delivery of diclofenac sodium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. Yong, CS., Choi, JS., Quan, QZ., et al.[2022]

A new liquid suppository system using sodium chloride and poloxamers was developed for diclofenac sodium, which was easier to administer and showed no leakage after insertion, unlike previous formulations with bioadhesive polymers that caused drug precipitation.

The liquid suppository demonstrated significantly higher initial plasma concentrations and faster absorption of diclofenac sodium compared to solid suppositories, indicating it is a more effective and convenient rectal dosage form.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository. Yong, CS., Choi, YK., Kim, YI., et al.[2019]

Topical gels made with sodium carboxymethylcellulose (NaCMC) for diclofenac sodium showed better drug release and skin permeation compared to commercial gel formulations, indicating improved efficacy for pain relief.

The study confirmed that NaCMC is biocompatible and does not interact negatively with diclofenac sodium, suggesting it is a safe and effective vehicle for delivering this medication through the skin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical permeation characteristics of diclofenac sodium from NaCMC gels in comparison with conventional gel formulations. Mohammed, FA.[2019]

Sodium butyrate significantly reduced colonic inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, as shown by improvements in disease activity index, colon length, and histopathology scores.

The treatment also preserved intestinal barrier integrity and altered the gut microbiota composition, suggesting that sodium butyrate may act through beneficial microbe-host interactions, highlighting its potential as a probiotic for colitis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Butyrate Alleviates Mouse Colitis by Regulating Gut Microbiota Dysbiosis. Dou, X., Gao, N., Yan, D., et al.[2020]

Butyrylated starch effectively delivers butyrate directly to the colon, enhancing butyrate and total short-chain fatty acid levels, which are beneficial for colitis treatment.

The use of butyrylated starch not only suppresses colitis symptoms but also reduces liver inflammation and hepatocyte damage, indicating a positive impact on overall gut health and the gut-liver axis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrylated starch protects mice from DSS-induced colitis: combined effects of butyrate release and prebiotic supply. Li, L., Cheng, L., Li, Z., et al.[2022]

A low intake of dietary fiber contributes to gut and metabolic health disorders by reducing the production of butyrate, a beneficial short-chain fatty acid that supports colonic health and systemic inflammation control.

Butyrate's effects on inflammation are more pronounced in the gut compared to peripheral tissues, likely due to higher concentrations in the gut, highlighting the importance of dietary fiber for maintaining gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. Bach Knudsen, KE., Lærke, HN., Hedemann, MS., et al.[2019]

Sodium butyrate (NaB) enhances TGF-beta signaling in gut epithelial cells, which may help explain how dietary fiber reduces the risk of colon cancer.

NaB not only induces the expression of Smad3 but also works together with TGF-beta to inhibit the growth of cancer cells, suggesting a potential therapeutic role in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fiber enhances a tumor suppressor signaling pathway in the gut. Nguyen, KA., Cao, Y., Chen, JR., et al.[2021]

Butyrate, a key microbial metabolite, has beneficial effects in colorectal cancer, including enhancing immune function, maintaining intestinal barrier integrity, and improving the effectiveness of anti-cancer treatments.

Sodium butyrate (NaB) shows promise as a supportive treatment for colorectal cancer patients, potentially reducing chemotherapy-induced mucositis and positively influencing gut microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium butyrate in both prevention and supportive treatment of colorectal cancer. Kaźmierczak-Siedlecka, K., Marano, L., Merola, E., et al.[2022]

Citations

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Study Details | NCT06419231 | Effectiveness of a Butyrate ... This is a double-blind, randomized, placebo-controlled, remote design study to evaluate the effects of a Butyrate formulation and Butyrate + Polyphenol ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11818678/

Health-Improving Effects of Polyphenols on the Human ... Consuming polyphenol-rich dietary fibers such as pomegranate, cranberry, berries, and tea improves gut health.

3. withpower.com withpower.com/trial/phase-gut-health-9-2023-38eb9

Butyrate and Polyphenols for Gut Health The available research shows that Butyrate and Polyphenols for Gut Health can be effective in treating conditions like colitis and colorectal cancer. For ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0144861725003224

The mutual effect of dietary fiber and polyphenol on gut ... This review explores how DF and polyphenols interact within the gut environment to influence microbial composition, promote beneficial metabolic ...

5. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1647740/full

Gut microbiome-mediated health effects of fiber and ... Polyphenol-rich foods, including strawberries, can enhance urolithin A production and increase abundances of SCFA-producing bacteria. For instance, daily ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9877435/

Butyrate producers, “The Sentinel of Gut”: Their intestinal ... Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0261561422003843

Butyrate's role in human health and the current progress ... Butyrate has also shown protective actions in the context of intestinal diseases such as inflammatory bowel disease, graft-versus-host disease of the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8747136/

Polyphenols—Gut Microbiota Interrelationship: A Transition to ... This review aims to investigate the prebiotic effect of polyphenols in preclinical and clinical studies, highlighting that the consumption of polyphenols leads ...

9. mdpi.com mdpi.com/1422-0067/26/3/1335

Health-Improving Effects of Polyphenols on the Human ... In this review, we provide a systematic overview of the effects of dietary polyphenols on the human gut microbiota and their impact on gut integrity and human ...