Butyrate + Exercise for Insulin Resistance

Overseen By Ryan Porter, Ph.D.

Age: 18 - 65

Sex: Male

Trial Phase: Academic

Sponsor: Texas Christian University

Must not be taking: Insulin, Antihypertensives, Antibiotics, Probiotics

Disqualifiers: Diabetes, Hypertension, Recent weight change, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how gut bacteria might alter the body's response to exercise, particularly in insulin use, which helps control blood sugar. It also examines whether sodium butyrate, a short-chain fatty acid supplement, can benefit those who do not see improvements from exercise alone. Participants will exercise five times a week and take the supplement in the final month. Men who are overweight, lead a sedentary lifestyle, and are part of TCU are encouraged to participate. This study could pave the way for more personalized exercise plans based on gut health to better manage blood sugar. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could lead to personalized health solutions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking insulin, antihypertensive medication, or weight loss medications.

What prior data suggests that this combination of butyrate and exercise is safe for improving insulin response?

Research has shown that butyrate, a natural supplement, may enhance the body's use of insulin, improving insulin sensitivity. Some studies have found that butyrate can prevent insulin resistance and obesity in animals on high-fat diets, suggesting potential benefits for people with similar issues.

However, not all results are positive. In some animal studies, butyrate has been linked to worse blood sugar control, indicating it may not work the same for everyone.

Currently, limited information exists on butyrate's effects on humans or its safety. As a natural supplement often used for gut health, it is generally considered safe in typical doses.

For those considering joining a trial with butyrate, it is important to understand that while potential benefits exist, results can vary. Consulting a healthcare provider ensures it is appropriate for individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for insulin resistance, like metformin or lifestyle changes, work by improving insulin sensitivity through various pathways. But sodium butyrate is unique because it targets the gut microbiome, fostering beneficial bacteria that can improve metabolic health. Researchers are excited about this approach because it combines the benefits of exercise with a naturally occurring compound, potentially offering a dual-action strategy to enhance insulin sensitivity. This combination could provide a more holistic and potentially more effective way to manage insulin resistance.

What evidence suggests that this trial's treatments could be effective for insulin resistance?

Research has shown that butyrate, a natural supplement, can help the body use insulin more effectively. This is especially beneficial for people with obesity who have insulin resistance. For instance, butyrate improves muscle response to insulin, boosting overall metabolic health. It may also help control blood sugar levels, making it useful for those who don't see improvements from exercise alone. In this trial, participants will undergo a 12-week exercise intervention, with sodium butyrate supplementation added during the final 4 weeks. The supplement influences gut bacteria, which can affect how the body manages insulin. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for males with overweight or obesity issues, interested in how exercise affects insulin use. Participants will engage in supervised exercise and take a gut health supplement. They must be willing to provide blood and stool samples, fill out questionnaires, and undergo body scans.

Inclusion Criteria

BMI ≥ 25.0 kg/m² (classified as overweight or obese)

Affiliated with TCU (student, staff, or faculty)

Sedentary lifestyle: less than 150 minutes/week of moderate-intensity aerobic activity, less than 75 minutes/week of vigorous-intensity activity, fewer than 1 strength training session/week over the past 6 months

Exclusion Criteria

Regular physical activity as defined in inclusion criteria

Participation in another research study (clinical trial or intervention study)

Recent significant weight change (≥5% of body weight lost or gained in the past 3 months)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exercise Intervention

Participants engage in a supervised cardiovascular exercise program, progressing from 30 to 60 minutes per session, 5 days per week, with intensity increasing from 50% to 80% of estimated maximum heart rate.

12 weeks

5 visits per week (in-person)

Supplementation

Participants take sodium butyrate supplementation during the last 4 weeks of the exercise program.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including collection of blood and stool samples, body composition scans, and completion of questionnaires.

4 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Butyrate

Trial Overview Researchers are testing if cardiovascular exercise improves insulin response in obese men, whether gut bacteria can predict the benefits of exercising, and if sodium butyrate supplements aid those who don't typically respond to exercise.

How Is the Trial Designed?

Group I: Exercise Experimental Treatment 2 Interventions

Participants will undergo a 12-week exercise intervention. During the final 4 weeks, they will additionally receive sodium butyrate supplementation. The model uses repeated measures to assess changes in insulin sensitivity, gut microbiome composition, and body composition before and after the intervention.

Who Is Running the Clinical Trial?

Texas Christian University

Lead Sponsor

Trials

31

Recruited

4,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2699871/

Butyrate Improves Insulin Sensitivity and Increases Energy ... These data suggest that butyrate is effective in the treatment of obesity and insulin resistance in the dietary obese model. FIG. 7. FIG. 7. Open in a new ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0925443922001478

Butyrate oxidation attenuates the butyrate-induced ... Recent data show that butyrate can improve metabolic health by vagal activation [19]. Skeletal muscle insulin sensitivity has also been shown to improve after ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07180446

Can Gut Bacteria Predict Who Benefits Most From Exercise ... The study also evaluates the effectiveness of sodium butyrate supplementation in enhancing insulin sensitivity among individuals who are otherwise non- ...

4. diabetesjournals.org diabetesjournals.org/diabetes/article/71/11/2438/147445/Butyrate-Producing-Bacteria-and-Insulin

Butyrate-Producing Bacteria and Insulin Homeostasis Comparison of the associations in each race with those of the combined cohort revealed the most consistent results for insulin sensitivity.

5. mdpi.com mdpi.com/2072-6643/17/11/1753

Effect of Sodium Butyrate Supplementation on Type 2 ... These findings suggest that butyrate may attenuate insulin resistance, dyslipidemia, and gluconeogenesis, thereby contributing to improved glucose homeostasis ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9541926/

Butyrate to combat obesity and obesity‐associated metabolic ... Butyrate might be able to prevent pancreatic dysfunction associated with the insulin‐resistant obese phenotype. Animal data indicate that butyrate may increase ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06247020

Metabolic Effects of Oral Sodium Butyrate Supplementation ... In particular, butyrate, in addition to its trophic action on enterocytes, could improve insulin sensitivity and increase GLP-1 secretion, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589936822000640

Sodium butyrate aggravates glucose dysregulation and ... A study in which offspring of dams fed with butyrate diet displayed insulin resistance indicated by elevated HOMA-IR and serum glucose level, suggests that ...

9. diabetesjournals.org diabetesjournals.org/diabetes/article/58/7/1509/15689/Butyrate-Improves-Insulin-Sensitivity-and

Butyrate Improves Insulin Sensitivity and Increases Energy ... On the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice.

10. insight.jci.org insight.jci.org/articles/view/166655

Dietary butyrate ameliorates metabolic health associated ... Particularly, butyrate was shown to prevent diet-induced obesity (DIO) (5), improve glucose homeostasis, and alleviate insulin resistance in ...