Researchers are testing whether a supplement called tributyrin, which comes from a natural substance in our gut, might help people with depression feel better. This small pilot study involves 24 people who will take the supplement for 8 weeks while continuing their regular depression medication. Scientists are checking whether the supplement is safe, easy to take, and if it might reduce depression symptoms. The study is based on new research showing that our gut bacteria and the chemicals they make may play a role in depression. If this small test works well, it could lead to a new type of treatment that works alongside traditional antidepressants.

The Quick Take

  • What they studied: Whether a supplement called tributyrin (a form of butyrate, a natural gut chemical) is safe, acceptable, and possibly helpful when added to regular depression medication
  • Who participated: 24 adults aged 18-65 years old who have been diagnosed with depression ranging from mild to severe, all currently taking antidepressant medication
  • Key finding: This is a pilot study, meaning it’s designed to test whether the research approach works before doing a larger study. Researchers will measure whether people can tolerate taking the supplement for 8 weeks and whether their depression symptoms improve
  • What it means for you: This research is still in early stages. If you have depression, don’t start taking tributyrin supplements yet based on this study alone. Talk to your doctor about whether participating in future research or waiting for larger studies might be right for you

The Research Details

This is a pilot randomized controlled trial, which is a type of research designed to test whether a new study approach actually works before investing in a larger, more expensive study. Half of the 24 participants will receive 4 grams of tributyrin daily for 8 weeks, while the other half will receive a placebo (a fake pill that looks identical). Neither the participants nor the researchers will know who gets the real supplement until the study ends—this is called “double-blind” and helps prevent bias.

Participants will track their depression symptoms weekly during the 8-week supplement period and then continue tracking for 16 weeks after stopping the supplement. They’ll also use a smartphone app to report their mood multiple times each day. Researchers will collect stool samples to examine gut bacteria, blood tests to check inflammation and other markers, and measure intestinal health.

The study is being conducted at Amsterdam University Medical Centre in the Netherlands and has been approved by a medical ethics committee, meaning experts have reviewed it to ensure it’s safe and ethical.

This research approach is important because depression is a serious condition affecting millions of people, and many people don’t respond well enough to current medications. Recent scientific discoveries suggest that our gut bacteria and the chemicals they produce may influence our mood and mental health through something called the “gut-brain axis.” By testing tributyrin in a controlled way, researchers can determine whether this approach is worth pursuing in larger studies. A pilot study is the smart first step because it’s smaller, faster, and cheaper than a full-scale trial, and it helps researchers work out any problems before investing more resources.

This study has several strengths: it’s randomized (meaning participants are randomly assigned to groups, reducing bias), it’s double-blind (neither participants nor researchers know who gets the real supplement), it includes a placebo control group (for fair comparison), and it’s registered in an international database before starting (which prevents researchers from hiding unfavorable results). However, 24 participants is a very small sample size, so results may not apply to everyone with depression. The study is also short-term (8 weeks of treatment), so we won’t know about long-term effects. This is intentionally a pilot study, so it’s designed to test feasibility rather than prove the supplement works.

What the Results Show

This is a study protocol paper, meaning it describes the plan for the research rather than reporting actual results. The study hasn’t been completed yet, so we don’t have data on whether tributyrin is feasible, acceptable, or effective. The researchers will measure feasibility by tracking how many people complete the study, how well they follow the protocol, and whether they experience side effects. Acceptability will be measured by asking participants about their experience with the supplement and whether they would recommend it to others.

Once the study is complete, researchers will analyze whether depression symptoms improved more in the tributyrin group compared to the placebo group. They’ll also examine changes in gut bacteria composition, inflammation markers, and other biological measures that might explain how the supplement could affect mood.

Beyond depression symptoms, the study will measure several other important outcomes. Researchers will track anhedonia (the inability to feel pleasure), which is a key symptom of depression. They’ll also monitor how the supplement affects the gut microbiome (the community of bacteria in our digestive system), inflammation levels in the body, and intestinal permeability (how easily substances pass through the intestinal wall). These measurements could help explain the biological mechanisms—the ‘why’ and ‘how’—behind any mood improvements.

This research builds on earlier laboratory studies showing that butyrate (the active ingredient in tributyrin) has antidepressant effects in animal models. However, very few human studies have tested butyrate supplementation for depression, which is why this pilot study is needed. The gut-brain axis is an emerging area of depression research, with growing evidence that gut bacteria influence mood through various chemical pathways. This study will be one of the first to rigorously test whether supplementing with butyrate can help people with depression in a controlled clinical setting.

This is a small pilot study with only 24 participants, so results may not apply to all people with depression. The 8-week treatment period is relatively short, so we won’t know about long-term safety or effectiveness. The study focuses on people aged 18-65 with mild-to-severe depression who are already taking antidepressants, so results may not apply to people outside this age range, those with very severe depression, or those not taking medication. Additionally, this is a feasibility study, not a full efficacy trial, so it’s not designed to prove the supplement works—only to test whether a larger study is possible. The study hasn’t been completed yet, so all results are still pending.

The Bottom Line

At this stage, there is insufficient evidence to recommend tributyrin supplementation for depression outside of research studies. This is a pilot study still in progress, and we need to wait for results before making any recommendations. If you have depression, continue working with your healthcare provider on proven treatments like antidepressant medication, therapy, exercise, and lifestyle changes. If you’re interested in gut health and mental health, discuss with your doctor about maintaining a healthy diet rich in fiber, which naturally supports beneficial gut bacteria. Do not start taking tributyrin supplements on your own, as safety and effectiveness in humans haven’t been established yet.

This research is most relevant to people with depression who haven’t fully responded to current treatments and are interested in new therapeutic approaches. It’s also important for mental health professionals, psychiatrists, and researchers exploring the gut-brain connection. People with severe depression, those under 18 or over 65, and those with certain gastrointestinal conditions should consult their doctor before considering any new supplements. If you’re pregnant, nursing, or taking medications that affect gut bacteria, talk to your healthcare provider before considering any butyrate supplements.

This is a pilot study, so results won’t be available immediately. The study involves 8 weeks of supplementation plus 16 weeks of follow-up, meaning it will take at least 6 months to collect data from all participants. After data collection, researchers need time to analyze results and publish findings, which typically takes several more months. Even if this pilot is successful, a larger, full-scale study would be needed before tributyrin could become a standard treatment. Realistically, it could be 2-3 years or more before we have clear answers about whether this supplement helps depression.

Want to Apply This Research?

  • Track daily mood scores (using a 1-10 scale) and note any changes in depression symptoms, energy levels, and ability to enjoy activities. Record any gastrointestinal changes (bloating, gas, bowel regularity) to monitor for side effects. If using the app, enable daily mood check-ins at consistent times to build a reliable data pattern.
  • If participating in this research or similar studies, use the app to set daily reminders to take the supplement at the same time each day, improving compliance. Log mood patterns before, during, and after supplementation to identify any correlations. Share weekly summaries with your healthcare provider to track progress and discuss any concerns.
  • Establish a baseline of your current mood, energy, and gastrointestinal symptoms before starting any supplement. Use the app to track these metrics consistently throughout the study period and during the follow-up phase. Create a simple weekly summary to share with your doctor, noting any improvements, side effects, or concerns. Continue tracking for at least 16 weeks post-supplementation to understand long-term effects.

This article describes a research study protocol that has not yet been completed. No clinical results are available yet. This information is for educational purposes only and should not be used to make medical decisions. Tributyrin supplementation has not been proven safe or effective for treating depression in humans. If you have depression, please work with a qualified mental health professional or physician before starting any new supplements or changing your treatment plan. Do not stop taking prescribed antidepressant medication without consulting your doctor. This research is still in early stages, and larger studies are needed before any recommendations can be made. Always consult with your healthcare provider before beginning any new supplement, especially if you are pregnant, nursing, taking medications, or have existing health conditions.