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Tributyrin (glyceryl tributyrate, butyrate prodrug)
Sold on a pharmacokinetic story — that esterifying butyrate into a triglyceride delivers it past the stomach to the distal colon. Only three human studies of tributyrin exist, totalling 50 participants, NONE of them placebo-controlled, and none met an efficacy endpoint. The delivery claim itself is unsubstantiated and partly contradicted.
What the evidence says
Most Tributyrin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 1998–2026 with a typical study size of 17 participants.
Based on 11 studies · 1 RCT · 62 total participants
Confidence
Low confidenceBy outcome
Three human studies exist, totalling 50 participants, none placebo-controlled, none blinded, and none meeting an efficacy endpoint. The distal-delivery premise the product is sold on is not just unproven but partly contradicted — tributyrin was rapidly cleaved in the stomach compartment of a gut model, and in rodents plain oral sodium butyrate reached far higher plasma butyrate than tributyrin did. Everything else is cells, mice and a registered protocol with no results.
9 trials ongoing or recruiting · 6 completed on ClinicalTrials.gov
1 of the completed trials have posted results
Registered trials show research momentum for Tributyrin, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Sep 2026
Tributyrin is the most heavily marketed and least clinically tested compound in the butyrate category, and the gap between those two facts is the whole story.
The human record consists of three studies: a 1998 Phase I dose-escalation in 13 patients with solid tumours, a 2003 Phase I study of thrice-daily dosing in 20 patients, and a 2026 open-label target-engagement study in 14 people with Parkinson's disease plus 3 controls. Fifty participants in total.
None had a placebo arm. None had blinding. None met an efficacy endpoint.
The 1998 study found plasma butyrate had disappeared by 5 hours after a dose and — importantly — peak concentrations rose with dose overall (0 to 0.45 mM) though they did not increase in the three individual patients who had their dose escalated, alongside no consistent change in fetal haemoglobin, the biomarker it was chasing.
The 2003 study found no dose-limiting toxicity but also no objective responses, and reported a median butyrate concentration of 52 micromolar with considerable interpatient variability — at the bottom of, not below, the 50-100 micromolar range those authors cite for in vitro activity.
Their own stated conclusion is that 'levels associated with in vitro activity are achieved with three times daily dosing' in vitro.
The 2026 Parkinson's study is genuinely interesting on the mechanism — [11C]butyrate PET imaging confirmed organ-level target engagement — but it is open-label with no control group and no blinding, and the authors label the cognitive and motor findings exploratory while calling for placebo-controlled trials.
The central marketing claim deserves specific scrutiny. Tributyrin is sold on the premise that the triglyceride form survives the upper gut and delivers butyrate to the distal colon.
The one study that directly examined where the cleavage happens found tributyrin was rapidly broken down in the GASTRIC compartment of a validated gut model — the opposite of the claim — and the modified triglyceride designed to fix that problem, while it did raise circulating butyrate, affected no secondary metabolic outcome at all.
The rodent pharmacokinetics also run against the story: in mice, ORAL sodium butyrate produced peak plasma butyrate around 9 mM, whereas oral tributyrin peaked around 1.75 mM at a dose that killed roughly 10% of animals. Plain sodium butyrate outperformed the prodrug.
The remaining literature is cell and animal work — human visceral fat ex vivo where tributyrin was comparable to sodium butyrate rather than superior, a Caco-2 colon-cancer cell line where it was more potent, and a mouse model of ethanol-induced gut injury.
A registered pilot trial in depression is underway, which tells you there is an active research pipeline and nothing at all about whether it works.
One genuine advantage is worth stating: unlike GOS and FOS, tributyrin is not a FODMAP and is not fermented by gut bacteria, so it does not carry their gas-and-bloating trade-off.
Tributyrin is glycerol esterified with three butyrate molecules. The premise is that the neutral triglyceride survives the upper gut and releases butyrate further down. The one study that looked directly found the opposite: in a validated stomach-and-small-intestine model, tributyrin was rapidly cleaved in the GASTRIC compartment.
In the first Phase I study, plasma butyrate peaked between 15 minutes and 3 hours and had disappeared by 5 hours after a dose. This is why the tested regimen is three times daily rather than once — and why once-daily products are not reproducing any tested schedule.
[11C]butyrate PET imaging before and after 30 days of supplementation confirmed organ-specific changes in brain, liver, heart and gastrointestinal butyrate uptake. Target engagement means the compound reaches tissue — it is not evidence that reaching tissue helps.
In intact human visceral fat incubated ex vivo, tributyrin reduced LPS-induced inflammatory cytokine production — comparably to plain sodium butyrate, not better than it. In Caco-2 colon-cancer cells it was more potent than butyrate at inhibiting growth, but that is a cell line.
How Tributyrin works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
It does not. Tributyrin and sodium butyrate are different compounds with different pharmacokinetics, and in mice the plain salt reached higher plasma butyrate than the prodrug. Trials of sodium butyrate in IBS and inflammatory bowel disease are evidence about sodium butyrate.
The one study in this population was open-label with no control group and no blinding. The authors themselves describe the clinical findings as exploratory and call for larger placebo-controlled trials. Treat it as a target-engagement result, not a treatment.
Both Phase I studies were in patients with advanced solid tumours and neither produced an objective response. There is no basis for using tributyrin as a cancer treatment or adjunct.
No data. The entire human evidence base is 50 people across three uncontrolled studies.
THEORETICAL AND IN VITRO ONLY — no action needed. In human colon-cancer cell lines, tributyrin's antiproliferative effect was enhanced by physiological concentrations of dihydroxycholecalciferol, attributed to tributyrin-induced overexpression of the vitamin D receptor (1.5-fold increased binding, no change in affinity). It is listed here only so that a frequently-cited cell-culture result is not mistaken for a human finding: the entire human tributyrin evidence base is roughly 50 people across three uncontrolled studies.
Tip: A specifically reported adverse event in the Phase I dose-escalation study; butyrate is the compound behind rancid-butter smell. No mitigation has been tested
Tip: Reported at the oncology doses of 50-400 mg/kg/day, far above the 1.5 g/day supplement dose. Reduce the dose or take with food
Tip: Grade 3 toxicities in the Phase I oncology study at doses up to 400 mg/kg/day — roughly 20-fold higher than the supplement dose. Discontinue and consult a clinician
The current evidence for Tributyrin is insufficient to assign an evidence score, based on 11 indexed studies. Sold on a pharmacokinetic story — that esterifying butyrate into a triglyceride delivers it past the stomach to the distal colon. Only three human studies of tributyrin exist, totalling 50 participants, NONE of them placebo-controlled, and none met an efficacy endpoint. The delivery claim itself is unsubstantiated and partly contradicted. Representative study: PMID 36687671.
The commonly studied dose of Tributyrin is 500 mg three times daily (1.5 g/day) — the only supplement-realistic dose ever tested in humans, used in the 30-day open-label Parkinson's study. Three times daily is not optional: plasma butyrate is gone by 5 hours after a dose, which is precisely why the second Phase I study abandoned once-daily dosing. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Tributyrin is in split doses through the day. It can be taken on an empty stomach. Spread across three doses because plasma butyrate is undetectable by 5 hours after a dose — a once-daily product cannot reproduce any tested exposure.
Tributyrin is generally safe at recommended doses, with a few precautions worth noting. The most commonly reported side effects are odour (on breath, skin or stool), nausea, abdominal cramping and diarrhoea, vomiting and myalgia. Use caution if any of these apply to you: None established — but note that no safety study has ever run longer than 30 days at supplement doses.
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Reviewed by Dr. Baher Al Hakim · Last reviewed July 2026 · evidence from 11 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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