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

Trial Summary

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.

What data supports the idea that Butyrate and Polyphenols for Gut Health is an effective treatment?

The available research shows that Butyrate and Polyphenols for Gut Health can be effective in treating conditions like colitis and colorectal cancer. For instance, sodium butyrate, a form of butyrate, has been shown to reduce inflammation in colitis by improving gut health and altering gut bacteria in mice. Another study found that butyrylated starch, which releases butyrate in the colon, helped reduce colitis symptoms and liver inflammation in mice. Additionally, sodium butyrate has been noted for its potential in supporting colorectal cancer treatment by maintaining gut health and enhancing the effectiveness of cancer therapies. These findings suggest that butyrate-based treatments can be beneficial for gut-related health issues. ^{1 2 3 4 5}

What safety data is available for Butyrate and Polyphenols for Gut Health treatment?

The provided research does not contain safety data for Butyrate and Polyphenols or any of their formulations. The studies focus on diclofenac sodium in various formulations and its safety and efficacy, not on Butyrate or Polyphenols. ^{6 7 8 9 10}

Is the treatment Butyrate Formulation, Butyrate + Polyphenol Formulation a promising treatment for gut health?

Yes, the treatment is promising for gut health. Sodium butyrate, a key component, is known to help reduce inflammation and support gut health. It can improve symptoms in conditions like inflammatory bowel disease and ulcerative colitis by promoting a healthy gut environment and reducing harmful inflammation. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this study is the assess the effectiveness and safety of a Butyrate formulation and a Butyrate + Polyphenol formulation on gut health, permeability and associated symptoms

Research Team

Andrew Swick, Ph.D

Principal Investigator

Life Extension

Eligibility Criteria

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.

I cannot provide urine, stool, or blood samples.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sodium Butyrate Alleviates Mouse Colitis by Regulating Gut Microbiota Dysbiosis. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Dietary fiber enhances a tumor suppressor signaling pathway in the gut. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Butyrylated starch protects mice from DSS-induced colitis: combined effects of butyrate release and prebiotic supply. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Sodium butyrate in both prevention and supportive treatment of colorectal cancer. [2022]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Japan pubmed.ncbi.nlm.nih.gov

Effect of polyol fatty acid esters on diclofenac permeation through rat skin. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. [2022]

10. United States 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. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. [2021]

13. China pubmed.ncbi.nlm.nih.gov

[Investigation of the effect of Na-butyrate on TNBS induced rat colitis]. [2013]

14. United States 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. [2023]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. [2019]