Tributyrin (CoreBiome® Butyrate Prodrug)

Tributyrin (glycerol tributyrate, glyceryl tributyrate)
Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Tributyrin is a triglyceride of three butyrate molecules on a glycerol backbone — a butyrate prodrug that resists gastric acid and is hydrolyzed by pancreatic lipase to release butyrate further down the GI tract. The pharmacokinetic point: free butyrate (sodium butyrate) is absorbed in the upper GI before reaching the colon, while in a laboratory digestion model roughly 50 to 60 percent of a tributyrin dose survived to enter the colon. Commercialized as CoreBiome® by Compound Solutions. Most CoreBiome evidence is in vitro (a SHIME gut simulator), and the only registered human trial of CoreBiome itself was terminated for loss of funding. Generic tributyrin has been given to people in a few small early-phase and open-label studies, but none was a placebo-controlled trial of gut health.

Studied Dose 300 to 1,000 mg/day with meals is the CoreBiome label range; no dose of CoreBiome has been tested for benefit in people.
Active Compound Tributyrin — triglyceride of glycerol + 3 butyric acid molecules; hydrolyzed by pancreatic lipase to free butyrate + glycerol. Distinct from sodium butyrate (free butyrate salt, rapidly absorbed).

Benefits

Colonic butyrate delivery vs free butyrate (laboratory gut simulator, not people)

In a Triple-L-SHIME laboratory gut simulator (glassware seeded with stool from three healthy adult male donors, with no people involved), the capsule formulation was 40.9% hydrolyzed in the small intestine with 59.1% reaching the colon (softgel: 48.7% / 51.3%). By contrast, free butyrate (sodium butyrate) is rapidly absorbed in the upper GI and very little reaches the colon — the underlying rationale for using a triglyceride prodrug instead of free butyrate.

Microbiome and inflammation effects (in vitro)

In the same Triple-L-SHIME® + Caco-2/THP1 co-culture model, daily tributyrin increased butyrate production, shifted the bacterial community, with increases reported in Bifidobacterium longum and Akkermansia muciniphila rather than in butyrate-producing species, increased IL-10, decreased TNF-α in the proximal colon while IL-1β, another pro-inflammatory marker, went up there, and protected against inflammation-induced intestinal barrier disruption. Effects emerged later in the treatment period, suggesting longer-term administration matters. All findings are in vitro — human translation is not yet established.

Postbiotic concept

Tributyrin is often marketed as a postbiotic because it delivers butyrate, a bacterial fermentation product, without needing a fiber substrate or live bacteria. Strictly, that label is wrong: the ISAPP consensus definition covers preparations of inanimate microorganisms or their components, and it specifically excludes purified metabolites such as butyrate, which ISAPP says should be called by their chemical names instead. Tributyrin is often suggested for people with low fiber tolerance or low microbial diversity, though no trial has tested whether it helps that group.

Colonocyte energy substrate

Textbook physiology holds that butyrate is the primary energy source for colonocytes, supplying roughly 60 to 70 percent of their energy, which is background about colonic butyrate in general rather than a finding about tributyrin. Adequate colonic butyrate supports normal colonic epithelial cell function. Whether oral tributyrin meaningfully increases colonocyte butyrate availability in humans has not been demonstrated in clinical trials.

Stomach-acid resistance and odorless formulation

The triglyceride form resists gastric acid degradation and is odorless — addressing two practical limitations of free butyrate (sodium butyrate has an unpleasant odor and is degraded/absorbed before reaching the colon). Formulation advantage rather than efficacy claim.

Mechanism of action

1

Pancreatic lipase hydrolysis to colonic butyrate

The triglyceride structure resists gastric acidity. Pancreatic lipase in the small intestine hydrolyzes tributyrin to release butyrate progressively, allowing a portion to reach the colon. This is the distinguishing pharmacokinetic advantage over free butyrate salts.

2

HDAC inhibition by butyrate

Butyrate inhibits histone deacetylases (HDACs), modifying gene expression with anti-inflammatory effects in cell and animal models. The HDAC mechanism applies to butyrate generally — not specific to tributyrin.

3

Tight junction integrity and NF-κB anti-inflammatory effects

Butyrate enhances tight junction protein expression (claudins, occludin, ZO-1) in intestinal epithelium and downregulates NF-κB-mediated inflammation, with corresponding effects reported in Caco-2/THP1 co-cultures.

4

GPR41 / GPR43 short-chain fatty acid receptor activation

Butyrate activates GPR41 (FFAR3) and GPR43 (FFAR2) on enteroendocrine cells, immune cells, and adipocytes, which in laboratory models modulates GLP-1 and PYY release and immune signaling. That is standard butyrate biology and it has not carried over to tributyrin in people: in a randomized crossover meal study in 12 healthy men, tributyrin produced no rise in GLP-1, PYY, GIP or cholecystokinin, no better than a carrot control, while olive oil and a C8 oil did raise GLP-1.

Clinical trials

1
CoreBiome Tributyrin in a SHIME Gut Simulator and Caco-2/THP1 Cells (In Vitro, No People)

Duysburgh C, Verstrepen L, Van Meulebroek L, Marzorati M. Frontiers in Nutrition 2025;12:1712993. A laboratory gut simulator study, not a trial in people.

Not a clinical population. This entry produced no human outcome data.

Duysburgh et al. 2025, Frontiers in Nutrition 12:1712993. No people took part. Upper GI tract simulation + Triple-L-SHIME® gut model with 3 healthy donor microbiomes + Caco-2/THP1 co-cultures. Capsule (300 mg) and softgel (450 mg) CoreBiome® formulations. Capsule: 40.9% small-intestinal hydrolysis, 59.1% colonic delivery. Softgel: 48.7% / 51.3%. Increased butyrate, increased Bifidobacterium longum and Akkermansia muciniphila, neither of them a butyrate producer, increased IL-10, decreased TNF-α, protection from inflammation-induced barrier disruption. In vitro evidence only, pivotal for the ingredient but not human. The study was funded by Compound Solutions, the CoreBiome supplier, and carried out by the contract laboratory ProDigest, which employs all four authors.

2
NCT06501898 — CoreBiome® FSU 4-Week Crossover Clinical Trial (terminated)

Florida State University randomized triple-masked crossover trial, planned 300 mg/day CoreBiome® for 4 weeks in sedentary adults with outcomes including metabolite concentrations, gut permeability, inflammation, sleep, and performance.

Sedentary adults were planned, but the trial was terminated and no participant results were ever reported.

No results exist from this trial. It was terminated for loss of funding before any outcome data was published, so it shows nothing about what CoreBiome does in people. As planned it was a Florida State University randomized triple-masked crossover trial of 300 mg/day CoreBiome for 4 weeks in sedentary adults, with outcomes including metabolite concentrations, gut permeability, inflammation, sleep, and performance. This was the only registered human clinical trial of CoreBiome®.

3
Tributyrin in Laboratory Cancer Research (No Benefit Shown in People)

Heidor R, Ortega JF, de Conti A, Ong TP, Moreno FS. Anticarcinogenic actions of tributyrin, a butyric acid prodrug. Current Drug Targets 2012;13(14):1720-1729. A narrative review of cell and animal work, not a trial.

Not applicable. This is a review of cell and animal studies, not a study in people.

Heidor R et al. 2012, Curr Drug Targets 13:1720-1729. A narrative review of tributyrin research in cancer cell lines and animal models. It is not limited to colorectal cancer. Tributyrin has been given to cancer patients in two early phase I studies, and the larger of them reported no objective tumor responses in 20 people. Nothing here supports taking tributyrin to prevent or treat any disease; this entry exists only so readers are not misled by the preclinical cancer literature.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated; food-grade glyceride source.
GI upset, mild diarrhea (occasional, especially at higher doses). At the far higher gram-level doses used in early cancer studies, nausea, vomiting and muscle pain were reported and were sometimes severe.
Mild bitter/rancid taste (less than free butyrate).
Pregnancy/lactation: limited specific data; precautionary avoidance.
Long-term safety: limited extended-trial human data.
Allergic reactions (rare).
Industry-sponsorship (Compound Solutions for CoreBiome®) — important context.

Important Drug interactions

Most medications: well-tolerated combination profile.
Pancreatic enzyme deficiency: reduced hydrolysis efficiency — consider digestive enzymes.
Antibiotics: may reduce gut-microbiome-mediated effects (but tributyrin is direct butyrate source, not microbiome-dependent).
Anti-inflammatory medications: no interaction has been studied. Talk to your doctor before adding tributyrin if you are being treated for a diagnosed bowel condition.
Antidiabetic medications: no interaction has been studied, and tributyrin has not been shown to change blood sugar or gut hormones in people.

Frequently asked questions about Tributyrin (CoreBiome® Butyrate Prodrug)

What is Tributyrin?

Tributyrin is a triglyceride of three butyrate molecules on a glycerol backbone — a butyrate prodrug that resists gastric acid and is hydrolyzed by pancreatic lipase to release butyrate further down the GI tract.

What is Tributyrin used for?

Tributyrin is researched primarily for Gut Health and Anti-Inflammatory. In a Triple-L-SHIME laboratory gut simulator (glassware seeded with stool from three healthy adult male donors, with no people involved), the capsule formulation was 40.9% hydrolyzed in the small intestine with 59.

What is the recommended dosage of Tributyrin?

The clinically studied dose is 300 to 1,000 mg/day with meals is the CoreBiome label range; no dose of CoreBiome has been tested for benefit in people. Always follow the product label and check with a healthcare provider for personal advice.

Is Tributyrin safe, and does it have side effects?

For most healthy adults, Tributyrin is well tolerated at studied doses. Reported effects can include: Generally well-tolerated; food-grade glyceride source. GI upset, mild diarrhea (occasional, especially at higher doses). At the far higher gram-level doses used in early cancer studies, nausea, vomiting and muscle pain were reported and were sometimes severe. It may also interact with some medications. Tributyrin is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Tributyrin interact with any medications?

Possible interactions include: Most medications: well-tolerated combination profile. Pancreatic enzyme deficiency: reduced hydrolysis efficiency — consider digestive enzymes. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Tributyrin?

NutraSmarts rates the evidence for Tributyrin as Limited (2 out of 5). It is backed by 3 clinical trials and 8 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(8 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Duysburgh C, Verstrepen L, Van Meulebroek L, Marzorati M Tributyrin (CoreBiome®) enhances butyrate levels and modulates the gut microbiota, barrier function, and immune response in vitro Front Nutr. 2025;12:1712993. doi:10.3389/fnut.2025.1712993.PubMedUsed to support: In vitro study using the SHIME® colonic model and Caco-2/THP1 co-cultures showing CoreBiome® tributyrin significantly elevates colonic butyrate, modulates gut microbiota composition, reinforces epithelial barrier integrity, and reduces inflammatory markers; supports colonic butyrate delivery and barrier findings in glassware only, with no human participants. Funded by Compound Solutions, the CoreBiome supplier, and carried out by ProDigest, which employs all four authors.
  2. Cresci GA, Bush K, Nagy LE Tributyrin supplementation protects mice from acute ethanol-induced gut injury Alcohol Clin Exp Res. 2014;38(6):1489-1501. doi:10.1111/acer.12428.PubMedUsed to support: Mouse study in which tributyrin preserved tight junction proteins in the ileum and proximal colon after ethanol exposure, and reduced liver enzyme and inflammatory rises after acute or short-term ethanol but not after chronic ethanol feeding. It did not measure colonocyte energy use. Animal evidence only, in ethanol-exposed mice.
  3. Korenblik V, Korosi A, Brul S, Bockting C, Nieuwdorp M, Lok A Feasibility and acceptability of 8-week oral tributyrin supplementation as add-on to antidepressant medication in patients with depression: a study protocol paper for a pilot, randomised controlled trial BMJ Open. 2025;15(11):e108423. doi:10.1136/bmjopen-2025-108423.PubMedUsed to support: Human RCT protocol (pilot feasibility trial) testing 8-week oral tributyrin supplementation via gut-brain axis in patients with depression; documents only that a human trial is planned. A protocol reports no results, so it can support no effect of tributyrin on anything. The dose planned there, 4 g/day, is several times the CoreBiome label amount.
  4. Bohnen JLB, Roytman S, Wigstrom TP, et al. Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study. Neurotherapeutics. 2026;23(1):e00791..PubMedUsed to support: Open-label with no placebo and no control arm: 14 people with Parkinson's disease and 3 controls took 500 mg tributyrin three times daily, 1.5 g/day, for 30 days. Carbon-11 butyrate PET imaging in 10 subjects confirmed organ-specific changes in butyrate uptake, and high-sensitivity CRP fell 34.9 percent (p = 0.002) in 13 participants. This is the only human evidence that tributyrin measurably moves an inflammatory marker, so it is the sole human support for the anti-inflammatory category, and it disproves any statement that tributyrin has never been tested in people. It is uncontrolled, very small, in a disease population, at a dose above this page's label range and not the CoreBiome product, so it caps the evidence at limited. Cognitive and motor changes were exploratory and uncontrolled and are not a benefit claim for a supplement.
  5. Conley BA, Egorin MJ, Tait N, et al. Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. Clin Cancer Res. 1998;4(3):629-34..PubMedUsed to support: Human pharmacokinetic evidence that oral tributyrin does raise plasma butyrate, but only briefly: peak concentrations of 0 to 0.45 mM within 0.25 to 3 hours, in 13 patients at 50 to 400 mg/kg/day. It is also the only human high-dose tolerability data, reporting grade 3 nausea, vomiting and muscle pain at these gram-level doses along with grade 1 and 2 diarrhea, headache and abdominal cramping, which is the basis for the added safety note. No efficacy benefit was shown.
  6. Edelman MJ, Bauer K, Khanwani S, et al. Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug. Cancer Chemother Pharmacol. 2003;51(5):439-44..PubMedUsed to support: Twenty patients with advanced solid tumors took tributyrin at 150 to 200 mg/kg three times daily. It was tolerated with no dose-limiting toxicity and reached a median plasma butyrate of 52 micromolar with wide variation between patients, but no objective tumor responses were seen. This is the human counterweight to the preclinical cancer literature in the third trial card and the basis for that card stating plainly that no benefit has been shown in people.
  7. Mandøe MJ, Hansen KB, Hartmann B, et al. The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans. Am J Clin Nutr. 2015;102(3):548-55..PubMedUsed to support: Randomized crossover meal study in 12 healthy men comparing tributyrin, a C8 oil, olive oil and carrots alone. Tributyrin produced no increase in any measured gut hormone, including GLP-1, PYY, GIP and cholecystokinin, performing the same as the plain carrot control, while olive oil and the C8 oil raised GLP-1. Human evidence directly against this page's GPR41 and GPR43 gut hormone mechanism as applied to tributyrin, and the reason metabolic health is removed as a measured-and-null category rather than merely caveated.
  8. Heidor R, Ortega JF, de Conti A, et al. Anticarcinogenic actions of tributyrin, a butyric acid prodrug. Curr Drug Targets. 2012;13(14):1720-9..PubMedUsed to support: Narrative review of tributyrin in cancer cell lines and animal models, not restricted to colorectal cancer. Included as context only; nothing in it supports taking tributyrin to prevent or treat any disease.