Tributyrin for Health and Performance

(CoreBiome Trial)

Overseen By Michael Ormsbee

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Florida State University

Must not be taking: Microbiome supplements

Disqualifiers: Metabolic, cardiovascular, gastrointestinal, others

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if tributyrin supplementation improves metabolite concentrations, overall health biomarkers, and performance in sedentary men and women. The study would further understand the potential usage of tributyrin as a health and performance increasing supplement through improving gut and immune health, sleep, and performance as well as reduce inflammation. Participants will supplement for tributyrin for 4 weeks and complete fecal metabolite measures, cardiovascular evaluation, sleep assessment, and exercise testing as well as provide blood samples.

Do I have to stop taking my current medications?

The protocol does not specify if you need to stop taking your current medications. However, you cannot take supplements that impact the microbiome, hydration, core temperature, or exercise performance.

What data supports the idea that Tributyrin for Health and Performance is an effective drug?

The available research shows that Tributyrin is effective in several ways. In studies on colon cancer cells, Tributyrin was more effective than natural butyrate in stopping cell growth and helping cells mature. It also worked well with vitamin D to boost these effects. In gastric and pancreatic cancer cells, Tributyrin was shown to stop growth and cause cell death. Compared to sodium butyrate, Tributyrin was more effective in slowing down the growth of colon cancer cells and helping them mature. Additionally, when Tributyrin was encapsulated and tested in a lab setting, it increased the production of butyrate, which is beneficial for gut health. These findings suggest that Tributyrin is a promising option for treating certain types of cancer and improving gut health. ^{1 2 3 4 5}

What safety data exists for Tributyrin treatment?

The provided research does not directly address safety data for Tributyrin in humans. However, studies on animals suggest potential benefits and effects. In mice, Tributyrin improved metabolic and inflammatory profiles without reported adverse effects. In broilers and piglets, it enhanced growth performance and modulated gut microbiota, again without noted safety concerns. These findings suggest Tributyrin may be safe, but human-specific safety data is not provided. ^{2 6 7 8 9}

Is the drug Tributyrin a promising treatment for health and performance?

The information provided does not include any research or studies about Tributyrin, so we cannot determine if it is a promising treatment for health and performance based on this data. ^{10 11 12 13 14}

Eligibility Criteria

This trial is for sedentary men and women who may have metabolic disorders, leaky gut syndrome, inflammation issues, sleep disturbances or performance anxiety. Participants will be required to take supplements and undergo various health assessments over a 4-week period.

Inclusion Criteria

Sedentary (<150 minutes of aerobic exercise per week)

I am between 30 and 50 years old.

Exclusion Criteria

Consumption of supplements known to impact the microbiome, hydration status, core temperature, or exercise performance

Experienced previous heat illness

Known injuries that limit exercise

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tributyrin supplementation for 4 weeks and complete fecal metabolite measures, cardiovascular evaluation, sleep assessment, and exercise testing as well as provide blood samples.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tributyrin (Short-Chain Fatty Acid)

Trial Overview The study tests whether tributyrin (CoreBiome) can improve metabolite concentrations, overall health biomarkers, and performance compared to a placebo. It involves fecal metabolite measures, cardiovascular evaluation, sleep assessment, exercise testing and blood samples.

Participant Groups

Group I: CoreBiome Active Control 1 Intervention

Participants will be given tributyrin (as CoreBiome)

Group II: Placebo Placebo Group 1 Intervention

Participants will be given a taste-, color-, and odor-matched placebo

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Compound Solutions Inc.

Collaborator

Trials

5

Recruited

250+

Compound Solutions Inc.

Industry Sponsor

Trials

5

Recruited

250+

Findings from Research

Tributyrin, a prodrug of butyrate, was found to be more effective than natural butyrate in inhibiting growth and promoting differentiation in Caco-2 colon cancer cells, suggesting it could be a better therapeutic option.

The combination of tributyrin and dihydroxycholecalciferol (a form of vitamin D) enhanced the effects on cancer cell growth and differentiation by increasing the expression of the vitamin D receptor, indicating a potential synergistic approach for colorectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tributyrin, a stable and rapidly absorbed prodrug of butyric acid, enhances antiproliferative effects of dihydroxycholecalciferol in human colon cancer cells. Gaschott, T., Steinhilber, D., Milovic, V., et al.[2018]

Tributyrin effectively inhibits the growth of human gastric cancer SGC-7901 cells in a dose- and time-dependent manner, significantly reducing DNA synthesis after 48 hours of treatment.

The mechanism of action involves inducing apoptosis in the cancer cells, as evidenced by changes in protein expression (decreased Bcl-2 and increased Bax), suggesting that tributyrin could be a promising agent for preventing and treating gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tributyrin inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest. Yan, J., Xu, YH.[2019]

Tributyrin and butyrate both effectively reduced the growth of human pancreatic cancer cells, with tributyrin showing a lower IC50 value (1.1 mmol/L) compared to butyrate (3.6 mmol/L), indicating it may be more potent.

Both compounds induced apoptosis and stimulated differentiation in pancreatic cancer cell lines, suggesting that tributyrin could be a promising therapeutic option for pancreatic cancer by achieving effective butyrate levels in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tributyrin, a butyrate precursor, impairs growth and induces apoptosis and differentiation in pancreatic cancer cells. Gaschott, T., Maassen, CU., Stein, J.[2012]

Tributyrin (TB) effectively inhibits the growth of HT-29 colon cancer cells in a dose-dependent manner, with an IC50 value of 1 mM, making it more potent than its active form, sodium butyrate, which has an IC50 of 2.2 mM.

TB not only suppresses cell proliferation but also promotes differentiation of cancer cells, as indicated by significant increases in the expression of markers like CEA and E-cadherin, suggesting its potential as a promising therapeutic agent for colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tributyrin induces growth inhibitory and differentiating effects on HT-29 colon cancer cells in vitro. Schröder, C., Eckert, K., Maurer, HR.[2019]

The study successfully encapsulated tributyrin (TB) with gamma-cyclodextrin (CD) using spray-drying, resulting in a complex that retains TB effectively and shows a crystalline structure, indicating a stable formulation.

In vitro tests demonstrated that the TB/CD complex significantly increased butyrate production in the ileum and ascending colon, suggesting its potential use in food applications to enhance gut health by delivering butyrate more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulation of tributyrin by gamma-cyclodextrin: Complexation, spray drying, and in vitro fermentation. Shi, X., Monaco, MH., Donovan, SM., et al.[2021]

In a study with diet-induced obese mice, treatment with tributyrin, a prodrug of butyrate, resulted in lower body weight gain and improved insulin sensitivity and glucose metabolism over six weeks.

Tributyrin treatment also led to an anti-inflammatory effect in adipose tissue, reducing pro-inflammatory markers and increasing anti-inflammatory markers, suggesting that targeting SCFA butyrate could be a promising strategy for addressing obesity-related metabolic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism. Sato, FT., Yap, YA., Crisma, AR., et al.[2023]

Tributyrin supplementation in yellow-feathered broilers improved growth performance, as indicated by a better feed conversion ratio and increased final weight compared to the control group, based on a study involving 360 chicks over 63 days.

The treatment with tributyrin also positively altered the intestinal microbiota, increasing beneficial bacteria like Bacteroidetes and correlating with improved feed efficiency, suggesting a mechanism of action through modulation of gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Dietary Tributyrin on Growth Performance, Biochemical Indices, and Intestinal Microbiota of Yellow-Feathered Broilers. Gong, L., Xiao, G., Zheng, L., et al.[2021]

Tributyrin supplementation in sows significantly shortened the total parturition time and reduced the diarrhea rate in suckling piglets, indicating improved reproductive performance and health outcomes.

The addition of tributyrin increased the diversity of gut microbiota in both sows and piglets, enhancing levels of beneficial bacteria like Lactobacillus, which may contribute to better immune responses and milk composition during lactation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal tributyrin supplementation in late pregnancy and lactation improves offspring immunity, gut microbiota, and diarrhea rate in a sow model. Lin, Y., Li, D., Ma, Z., et al.[2023]

Tributyrin, when added to the diet of weaning piglets at a concentration of 0.2%, significantly altered gut microbiota composition, increasing beneficial bacterial genera associated with growth performance.

The changes in gut microbiota were linked to improved average daily gain and body weight in piglets, suggesting that tributyrin may enhance energy metabolism while reducing carbohydrate metabolism, contributing to better growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Tributyrin on Gut Microbiota Shifts Related to Performances of Weaning Piglets. Miragoli, F., Patrone, V., Prandini, A., et al.[2021]

In a study involving 65 men with abnormal semen quality, treatment with Tribulus terrestris significantly improved sperm concentration, motility, and liquefaction time, indicating its potential as a therapeutic option for male infertility.

The treatment also led to a decrease in body fat percentage and an increase in lean muscle mass, alongside elevated levels of dihydrotestosterone, suggesting that Tribulus terrestris may enhance overall male reproductive health through its action on hormone levels and testicular function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oral administration of Tribulus terrestris extract on semen quality and body fat index of infertile men. Salgado, RM., Marques-Silva, MH., Gonçalves, E., et al.[2018]

In a study involving 15 resistance-trained males over 8 weeks, supplementation with Tribulus terrestris did not lead to significant changes in body composition or mood states compared to a placebo.

While the placebo group showed improvements in muscle endurance for both bench and leg press exercises, the tribulus group only demonstrated a significant increase in leg press strength, indicating that tribulus may not enhance overall exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of Tribulus terrestris on body composition and exercise performance in resistance-trained males. Antonio, J., Uelmen, J., Rodriguez, R., et al.[2022]

In a study of 70 aging males with erectile dysfunction, those who took Tribulus terrestris for 3 months showed significant increases in testosterone levels and improved erectile function, as measured by a validated index.

Despite some elevations in liver enzymes and prostate-specific antigen, there were no negative effects on lower urinary tract symptoms, indicating that Tribulus terrestris may be a safe option for improving sexual health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tribulus terrestris versus placebo in the treatment of erectile dysfunction and lower urinary tract symptoms in patients with late-onset hypogonadism: A placebo-controlled study. GamalEl Din, SF., Abdel Salam, MA., Mohamed, MS., et al.[2019]

Tribulus terrestris L. contains a variety of active compounds, including sterol saponins and flavonoids, which are believed to have potential health benefits for conditions like infertility, low libido, and diabetes, but the effectiveness can vary widely due to differences in composition and extraction methods.

Research on Tribulus terrestris has produced mixed results regarding its efficacy and safety, indicating a need for standardized extracts and further studies to confirm its pharmacological mechanisms and therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L. Ștefănescu, R., Tero-Vescan, A., Negroiu, A., et al.[2023]

Tribulus terrestris has a long history of use in traditional medicine for treating various conditions, particularly infertility and loss of libido, due to its active compounds like flavonoids and saponins.

The plant exhibits multiple pharmacological activities, including anti-inflammatory, antimicrobial, and antioxidant effects, suggesting its potential for broader therapeutic applications and warranting further research into its health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phytopharmacology of Tribulus terrestris. Shahid, M., Riaz, M., Talpur, MM., et al.[2017]

References

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

Tributyrin, a stable and rapidly absorbed prodrug of butyric acid, enhances antiproliferative effects of dihydroxycholecalciferol in human colon cancer cells. [2018]

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

Tributyrin inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Tributyrin, a butyrate precursor, impairs growth and induces apoptosis and differentiation in pancreatic cancer cells. [2012]

4. Greece pubmed.ncbi.nlm.nih.gov

Tributyrin induces growth inhibitory and differentiating effects on HT-29 colon cancer cells in vitro. [2019]

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

Encapsulation of tributyrin by gamma-cyclodextrin: Complexation, spray drying, and in vitro fermentation. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Dietary Tributyrin on Growth Performance, Biochemical Indices, and Intestinal Microbiota of Yellow-Feathered Broilers. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Maternal tributyrin supplementation in late pregnancy and lactation improves offspring immunity, gut microbiota, and diarrhea rate in a sow model. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Implications of Tributyrin on Gut Microbiota Shifts Related to Performances of Weaning Piglets. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Effect of oral administration of Tribulus terrestris extract on semen quality and body fat index of infertile men. [2018]

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

The effects of Tribulus terrestris on body composition and exercise performance in resistance-trained males. [2022]

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

Tribulus terrestris versus placebo in the treatment of erectile dysfunction and lower urinary tract symptoms in patients with late-onset hypogonadism: A placebo-controlled study. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L. [2023]

14. Italy pubmed.ncbi.nlm.nih.gov

Phytopharmacology of Tribulus terrestris. [2017]