Tributyrin

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Tributyrin
Tributyrin.svg
Tributyrin 3D ball.png
Names
Systematic IUPAC name
Propane-1,2,3-triyl tributanoate
Other names
Tributyrin; Glyceryl tributyrate; Glycerol tributyrate; Glycerin tributyrate; NSC-661583; CoreBiome; ButyraGen
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.000.410 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C15H26O6/c1-4-7-13(16)19-10-12(21-15(18)9-6-3)11-20-14(17)8-5-2/h12H,4-11H2,1-3H3
    Key: UYXTWWCETRIEDR-UHFFFAOYSA-N
  • CCCC(=O)OCC(COC(=O)CCC)OC(=O)CCC
Properties
C15H26O6
Molar mass 302.367 g·mol−1
AppearanceOily liquid with bitter taste [1]
Density 1.032 g/cm3 [1]
Melting point −75 °C (−103 °F; 198 K) [1]
Boiling point 305 to 310 °C (581 to 590 °F; 578 to 583 K) [1]
Insoluble [1]
Hazards
Safety data sheet (SDS) Tributyrin MSDS, Fischer Scientific
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Tributyrin, also known as glyceryl tributyrate, is a triglyceride (fat) naturally present in butter. [2] [3] [4] It is an ester composed of three butyric acid (butyrate) moieties and glycerol. [1] It can be described as a liquid fat with an acrid taste. About 3 to 4% of butter is tributyrin, with butter being the richest known food source of tributyrin. [3] [5] The compound is also used as a dietary supplement [6] [7] and is being studied for various potential medical uses [2] [8] [9] due to it being a slowly converted precursor or prodrug of the short-chain fatty acid and "postbiotic" butyric acid, which is a major product of beneficial gut bacteria. [10]

Contents

Pharmacology

Tributyrin is a precursor or prodrug of the endogenous short-chain fatty acid (SCFA) butyric acid (butyrate). [4] [2] [5] It is stable and is rapidly absorbed and gradually converted into butyric acid. [2] [5] [11] Tributyrin is not broken down by gastric juice and is slowly converted into butyric acid and glycerol by pancreatic lipases in the gut. [12] In addition, tributyrin is more lipophilic than butyric acid and is taken up into cells much more readily in comparison. [4] Butyric acid itself has an extremely short elimination half-life of seconds to minutes among other limitations, which makes its own use impractical. [2] [3] [13] [14] For comparison, tributyrin has considerably longer half-life of 40 minutes with oral administration in rodents. [2] [5]

Butyric acid, the active form of tributyrin, has a large variety of biological effects. [10] It is an agonist of the FFAR2 (GPR43), FFAR3 (GPR41), and GPR109A and a histone deacetylase (HDAC) inhibitor of HDAC classes I and II. [10] In addition, butyric acid is the preferred energy source for colonocytes, and has been found to provide approximately 70% of total energy needs for colonocytes in mice. [10] Butyrate plays a key role in gut homeostasis and has anti-inflammatory effects among others. [10] Tributyrin is described as an HDAC inhibitor similarly to butyric acid. [15] [16]

Tributyrin has been found to reverse gut microbiota dysbiosis and intestinal injury and inflammation induced by antibiotics in rodents. [4] [12] [17] This included increasing potentially beneficial SCFA-producing bacteria such as Muribaculaceae and Bifidobacterium and decreasing potentially pathogenic bacteria such as Bacteroidetes and Enterococcus . [12] One means by which SCFAs like butyrate may mediate such effects is by decreasing intestinal pH. [18] In accordance with the observed intestinal bacterial changes, tributyrin increased levels of the SFCAs butyric acid, acetic acid (acetate), and propionic acid (propionate). [12] The effects of tributyrin and butyrate appear to be dose-dependent, with low concentrations promoting the intestinal barrier and inhibiting inflammation while high concentrations can do the opposite via induction of apoptosis. [4] [12] In addition to reversing antibiotic-induced dysbiosis, tributyrin has been found to strongly reduce Clostridium difficile infection in rodents. [4] [19] Coadministration of tributyrin with the probiotics Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus has been found to synergistically increase butyrate levels in humans ex vivo as well. [20] [21]

Butyric acid is known to activate the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling pathway via its HDAC inhibition. [22] [23] Tributyrin has been found to modulate hippocampal synaptic plasticity and improve memory in rodents. [24] [25] It has also been found to enhance sleep and increase slow wave sleep (SWS) in rodents. [26] [27] [28] [29] [30] Beneficial effects of butyric acid on sleep in rodents have been found to be mediated by activation of the BDNF–TrkB pathway. [31]

The pharmacokinetics of tributyrin in rodents have been studied. [2] [5] [32] [33] [34] [35] In addition, tributyrin has been clinically studied in people with solid tumors. [13] [14] Oral administration of high doses of tributyrin (50–400 mg/kg) has been found to maintain elevated circulating butyrate levels for up to 4 hours. [2] [3] [13] [14] This was insufficient for once-daily administration, so thrice daily administration was subsequently pursued instead, though butyrate levels during therapy remained erratic. [2] [3] [13] [14] The elimination half-life of tributyrin in humans could not be determined due to levels being too erratic. [14] [13] On the other hand, its time to peak levels was median 2.75 hours and range 2.0 to 3.5 hours. [14] The time to peak levels for butyrate specifically (with tributyrin) is median 0.5 to 1.5 hours and range 0.5 to 4.0 hours. [14] [13]

Supplement

Tributyrin is sold as an over-the-counter supplement under names like CoreBiome, ButyraGen and TauBiotic among others and has been referred to as a "postbiotic"—that is, a microorganism metabolite that has biological effects and potentially therapeutic benefits. [6] [7] [36] [37] [9] [8] The compound has a mild, lingering odor and bitter taste, but this is overcome with supplements via formulation in soft gelatin capsules. [5] Tributyrin has greater encapsulation efficacy than sodium butyrate. [8] As a result, high doses of tributyrin can be contained in capsules than sodium butyrate—500 mg per capsule and 150 mg sodium butyrate per capsule. [8] The reduced number of capsules needed may make tributyrin more acceptable in comparison to sodium butyrate, in addition to its more favorable pharmacokinetic properties. [8]

Other uses

Tributyrin is used in microbiological laboratories to identify the bacterium Moraxella catarrhalis . [38]

Research

Tributyrin was under formal clinical development for the treatment of solid tumors in the late 1990s, but no further development was subsequently reported. [39] It is also being clinically studied in the treatment of depression (4 g/day) [8] and Parkinson's disease (1.5 g/day). [9] [40] [41] [42] In a preliminary phase 1b clinical trial for Parkinson's disease, tributyrin demonstrated target engagement (increased butyric acid levels in the brain and other organs), produced systemic anti-inflammatory effects, showed improvements in cognitive and motor symptoms, and increased deep sleep by about 22% or approximately 15 minutes per night. [43] [9] [40] [42] A larger phase 2 trial of tributyrin for Parkinson's disease, known as BUTTER2, is now underway. [9] [40] [42] [41] The proper dosage of tributyrin and butyrate for therapeutic use, based on extrapolation from endogenous intestinal butyrate production (~1–10 g/day), has been studied and reviewed. [8] [44]

See also

References

  1. 1 2 3 4 5 6 Budavari, Susan, ed. (1996). The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (12th ed.). Merck. ISBN   0911910123.
  2. 1 2 3 4 5 6 7 8 9 Heidor R, Ortega JF, de Conti A, Ong TP, Moreno FS (December 2012). "Anticarcinogenic actions of tributyrin, a butyric acid prodrug". Curr Drug Targets. 13 (14): 1720–1729. doi:10.2174/138945012804545443. PMID   23140283. Tributyrin (TB), a BA prodrug present in milk fat and honey, has more favorable pharmacokinetic properties than BA, and its oral administration is also better tolerated. [...] The butyrate half-life may be considerably increased when it is administered as its natural prodrug, namely tributyrin (TB) [37-39]. TB, which is found in a variety of foodstuffs such as milk fat and honey [40, 41], is a triacylglycerol composed of three BA molecules esterified with glycerol. Therefore, the full hydrolysis of 1 mole of TB may generate 3 moles of BA. After oral administration to rodents, the TB half-life was approximately 40 minutes [42]. In addition, the oral administration of TB to rodents produced detectable serum butyrate levels five minutes later, and the levels reached their peak 15 to 60 minutes after administration [39] and could be maintained above 0.1 mM for up to 120 minutes [39, 41]. [...] TB, the natural BA prodrug, is quickly absorbed into the serum and is chemically stable. The hydrolysis of TB gives rise to butyrate molecules that exert inhibitory effects on several types of cancer. [...]
  3. 1 2 3 4 5 Wächtershäuser A, Stein J (August 2000). "Rationale for the luminal provision of butyrate in intestinal diseases". Eur J Nutr. 39 (4): 164–171. doi:10.1007/s003940070020. PMID   11079736. A direct source of butyrate is the diet, where it is present at low levels in many fruits and vegetables, but its richest source is from milk fat (butter) which contains 3–4 % butyrate as glycerol esters, termed tributyrin [18]. [...]
  4. 1 2 3 4 5 6 Yu J, Li W, Xu Y, Tang J (June 2026). "Gut microbiota-derived short-chain fatty acids (SCFAs): immunomodulatory effects and therapeutic potential in infections". Clin Microbiol Rev e00368-25: e0036825. doi:10.1128/cmr.00368-25. PMID   42267834.
  5. 1 2 3 4 5 6 Newmark HL, Young CW (1995). "Butyrate and phenylacetate as differentiating agents: practical problems and opportunities". J Cell Biochem Suppl. 22: 247–253. doi:10.1002/jcb.240590831. PMID   8538206.
  6. 1 2 Duysburgh C, Verstrepen L, Van Meulebroek L, Marzorati M (2025). "Tributyrin (CoreBiome®) enhances butyrate levels and modulates the gut microbiota, barrier function, and immune response in vitro". Front Nutr. 12 1712993. doi: 10.3389/fnut.2025.1712993 . PMC   12746503 . PMID   41473189.
  7. 1 2 Smith, Morganne; Lelah, Michael; Goggans, Mallory; Tunio, Sameer; Naqib, Ankur; Burton-Freeman, Britt; Edirisinghe, Indika (2024). "Investigation of the tolerability and potential health benefits of a novel butyrate generating supplement in a pilot human study". Nutrition and Healthy Aging. 9 (1): 133–144. doi:10.3233/NHA-240005. ISSN   2451-9480 . Retrieved 7 July 2026.
  8. 1 2 3 4 5 6 7 Korenblik V, Korosi A, Brul S, Bockting C, Nieuwdorp M, Lok A (November 2025). "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. 15 (11) e108423. doi: 10.1136/bmjopen-2025-108423 . PMC   12587968 . PMID   41248397.
  9. 1 2 3 4 5 Bohnen JL, Roytman S, Wigstrom TP, Vangel RK, Barr JE, Carli G, Parks SM, Mittal H, Martino C, Kanel P, Albin RL, Bohnen NI (January 2026). "Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study". Neurotherapeutics. 23 (1) e00791. doi:10.1016/j.neurot.2025.e00791. PMC   12976542 . PMID   41271518.
  10. 1 2 3 4 5 Mukhopadhya I, Louis P (October 2025). "Gut microbiota-derived short-chain fatty acids and their role in human health and disease". Nat Rev Microbiol. 23 (10): 635–651. doi:10.1038/s41579-025-01183-w. PMID   40360779.
  11. ↑ Gaschott, Tanja; Steinhilber, Dieter; Milovic, Vladan; Stein, Jürgen (June 2001). "Tributyrin, a Stable and Rapidly Absorbed Prodrug of Butyric Acid, Enhances Antiproliferative Effects of Dihydroxycholecalciferol in Human Colon Cancer Cells". The Journal of Nutrition . 131 (6). Bethesda, MD: The American Society for Nutritional Sciences: 1839–1843. doi: 10.1093/jn/131.6.1839 . ISSN   1541-6100. PMID   11385076 . Retrieved 2009-08-17. In spite of its early promise, butyrate is not among the drugs used for cancer treatment. The major problem has been to achieve and maintain its millimolar concentrations in blood. Butyrate is metabolized rapidly as soon as it enters the colonocyte via its active transport system (11–13), and its plasma concentrations are far below those required to exert its antiproliferative/differentiating actions. A prodrug of natural butyrate, tributyrin, is a neutral short-chain fatty acid triglyceride that is likely to overcome the pharmacokinetic drawbacks of natural butyrate as a drug (14). Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. Compared with butyrate, tributyrin has more favorable pharmacokinetics (14–16) and is well tolerated (17). Liquid tributyrin filled into gelatin capsules and administered orally resulted in millimolar concentrations of butyrate both in plasma and inside the cell (17).
  12. 1 2 3 4 5 Yang N, Lan T, Han Y, Zhao H, Wang C, Xu Z, Chen Z, Tao M, Li H, Song Y, Ma X (2023). "Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice". PLOS ONE. 18 (7): e0289364. Bibcode:2023PLoSO..1889364Y. doi: 10.1371/journal.pone.0289364 . PMC   10389721 . PMID   37523400.{{cite journal}}: CS1 maint: article number as page number (link)
  13. 1 2 3 4 5 6 Conley BA, Egorin MJ, Tait N, Rosen DM, Sausville EA, Dover G, Fram RJ, Van Echo DA (March 1998). "Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors" (PDF). Clin Cancer Res. 4 (3): 629–634. PMID   9533530. Archived from the original on 7 July 2026.
  14. 1 2 3 4 5 6 7 Edelman MJ, Bauer K, Khanwani S, Tait N, Trepel J, Karp J, Nemieboka N, Chung EJ, Van Echo D (May 2003). "Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug". Cancer Chemother Pharmacol. 51 (5): 439–444. doi:10.1007/s00280-003-0580-5. PMID   12736763.
  15. ↑ Rocchi P, Tonelli R, Camerin C, Purgato S, Fronza R, Bianucci F, Guerra F, Pession A, Ferreri AM (June 2005). "p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells". Oncol Rep. 13 (6): 1139–1144. PMID   15870934.
  16. ↑ Gerunova LK, Gerunov TV, P'yanova LG, Lavrenov AV, Sedanova AV, Delyagina MS, Fedorov YN, Kornienko NV, Kryuchek YO, Tarasenko AA (March 2024). "Butyric acid and prospects for creation of new medicines based on its derivatives: a literature review". J Vet Sci. 25 (2) e23. doi:10.4142/jvs.23230. PMC   10990906 . PMID   38568825.
  17. ↑ Cresci G, Nagy LE, Ganapathy V (November 2013). "Lactobacillus GG and tributyrin supplementation reduce antibiotic-induced intestinal injury". JPEN J Parenter Enteral Nutr. 37 (6): 763–774. doi:10.1177/0148607113486809. PMC   3818407 . PMID   23630018. Providing butyrate can be challenging for several reasons, including short metabolic half-life, toxicity, and patient intolerance. Butyrate has been provided via several routes: intravenously, rectally as enemas, and orally. There are limitations to providing butyrate intravenously (500 mg/kg body weight) in that large volumes are required, and the metabolic half-life is very short, with blood levels peaking about 6 minutes after delivery.10 Providing higher rates of intravenous (IV) butyrate infusion is undesirable due to risk of toxicity from sodium overload. Rectal enemas (100 mmol/L) have been successful in reversing negative gastrointestinal (GI) effects in patients with inflammatory bowel disease; however, this mode of delivery lends to very poor patient compliance.10 Tributyrin overcomes many of the problems of the parent compound. Tributyrin delivered orally in animals has a plasma half-life of 40 minutes.16 In humans, oral delivery provided once daily for 3 weeks was without severe toxicity, and peak plasma butyrate concentrations occurred between 0.25 and 3 hours after dose and ranged from 0–0.45 mM, which is near those found to be effective in vitro (0.5–1 mM).22 [...] The fact that tributyrin alone was able to exhibit these beneficial effects is intriguing as many factors can impair efficacy of probiotic provision (eg, viability, dosing, timing, colonization, storage temperature). [...] If tributyrin supplementation alone achieves the desired outcomes of improved gut integrity and preservation of genes and proteins involved with water and electrolyte homeo-stasis, then this therapy may prove more attractive to clinicians and patients.
  18. ↑ Zhao X, Liu S, Li S, Jiang W, Wang J, Xiao J, Chen T, Ma J, Khan MZ, Wang W, Li M, Li S, Cao Z (April 2024). "Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals". Cell Metab. 36 (4): 725–744. doi:10.1016/j.cmet.2024.03.004. PMID   38569470. Another class of bioactive molecules found in postbiotics is the SCFAs, which include acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid.120 These SCFAs are predominantly absorbed in the large intestine of monogastric animals and the rumen of ruminants, providing a valuable energy source for the host. Organic acids and SCFAs within postbiotics contribute to a decrease in pH that leads to a shift in the GI tract, creating an environment conducive for the growth of beneficial bacteria, such as LAB and Bifidobacteria, while concurrently reducing the population of pathogens, including Enterobacteria and E. coli. 115 These findings have been consistently reported in numerous studies involving pigs and chickens. [...] Such findings consistently support the positive impacts of postbiotics on gut microbiota composition, favoring beneficial bacteria while suppressing pathogenic species.
  19. ↑ Ouyang ZR, Niu XR, Wang WG, Zhao JH (June 2022). "The role of short-chain fatty acids in Clostridioides difficile infection: A review". Anaerobe. 75 102585. doi:10.1016/j.anaerobe.2022.102585. PMID   35545183. Dietary interventions, supplementation with butyrate-producing bacteria, and tributyrin treatment increase butyrate production and improve CDI [18,29,41].
  20. ↑ Feng J, Cen Q, Cui Y, Hu X, Li M, Wang L, Wei J, Sun N, Wang J, Zhang A (January 2025). "Lactobacillus rhamnosus: An emerging probiotic with therapeutic potential for depression". Pharmacol Res. 211 107541. doi:10.1016/j.phrs.2024.107541. PMID   39653301. Supplementation with tributyrin (TB) significantly raises butyrate levels, and L. rhamnosus ATCC 53103 (LGG) may enhance butyrate production by modulating the gut microbiota [117].
  21. ↑ Van den Abbeele P, Goggans M, Deyaert S, Baudot A, Van de Vliet M, Calatayud Arroyo M, Lelah M (March 2023). "Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 Synergistically Boost Butyrate Levels upon Tributyrin Administration Ex Vivo". Int J Mol Sci. 24 (6): 5859. doi: 10.3390/ijms24065859 . PMC   10054277 . PMID   36982942.
  22. ↑ Korenblik V, Schilder NK, de Lange IG, Daams JG, Bockting CL, Brul S, Nieuwdorp M, Lok A, Korosi A (February 2026). "From gut to glee: Is butyrate a promising antidepressant? A systematic review and mechanistic insights". Brain Behav Immun. 132 106237. doi:10.1016/j.bbi.2025.106237. PMID   41429215.
  23. ↑ Kim HJ, Leeds P, Chuang DM (August 2009). "The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain". J Neurochem. 110 (4): 1226–1240. doi:10.1111/j.1471-4159.2009.06212.x. PMC   2726719 . PMID   19549282.
  24. ↑ Belén Sanz-Martos A, Fernández-Felipe J, Merino B, Cano V, Ruiz-Gayo M, Del Olmo N (June 2022). "Butyric Acid Precursor Tributyrin Modulates Hippocampal Synaptic Plasticity and Prevents Spatial Memory Deficits: Role of PPARγ and AMPK". Int J Neuropsychopharmacol. 25 (6): 498–511. doi:10.1093/ijnp/pyac015. PMC   9211015 . PMID   35152284.
  25. ↑ Sanz-Martos AB, Roca M, Ruiz-Gayo M, Del Olmo N (August 2024). "Tributyrin reverses the deleterious effect of saturated fat on working memory and synaptic plasticity in juvenile mice: differential effects in males and females". Eur J Pharmacol. 977 176726. doi:10.1016/j.ejphar.2024.176726. PMID   38852700.
  26. ↑ Wang Z, Wang Z, Lu T, Chen W, Yan W, Yuan K, Shi L, Liu X, Zhou X, Shi J, Vitiello MV, Han Y, Lu L (October 2022). "The microbiota-gut-brain axis in sleep disorders". Sleep Med Rev. 65 101691. doi:10.1016/j.smrv.2022.101691. PMID   36099873. Tributyrin, as a butyrate pro-drug, improved NREM sleep in rats, an effect mediated through the vagus in the hepatoportal region [110]. A recent study in young subjects showed that sleep quality was positively associated with higher relative abundance of butyrate-producing genera [111].
  27. ↑ Szentirmai É, Millican NS, Massie AR, Kapás L (May 2019). "Butyrate, a metabolite of intestinal bacteria, enhances sleep". Sci Rep. 9 (1) 7035. Bibcode:2019NatSR...9.7035S. doi:10.1038/s41598-019-43502-1. PMC   6504874 . PMID   31065013. Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%.
  28. ↑ Liu Y, Cai Y, Shi X, Fan M, Zhang X, Lin J, Fan X, Liu B, Pan J (January 2026). "Distinct Gut Microbiota Profiles Reflect Severity in Chronic Insomnia Disorder". Brain Behav. 16 (1) e71155. doi:10.1002/brb3.71155. PMC   12755969 . PMID   41476015. Importantly, intervention with tributyrin (a butyrate prodrug) suppressed orexin neuron activation and ameliorated sleep disturbances, suggesting that gut microbiota may contribute to sleep disorders through disrupted butyrate metabolism and impaired hypothalamic neuronal homeostasis (Wang et al. 2024). Furthermore, Szentirmai et al. reported that butyrate promotes NREM sleep in mice, potentially through sensory mechanisms located in the liver and/or portal vein system (2019). In a Parkinson's disease mouse model, butyrate supplementation was shown to restore normal sleep architecture, possibly via the BDNF‐TrkB signaling pathway (Duan et al. 2025).
  29. ↑ Wang Z, Wang Z, Lu T, Yuan G, Chen W, Jin J, Jiang X, Yan W, Yuan K, Zou G, Bao Y, Shi J, Liu X, Wei H, Han Y, Lu L (June 2025). "Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis". Mol Psychiatry. 30 (6): 2597–2611. doi:10.1038/s41380-024-02867-0. PMID   39658705.
  30. ↑ Duan WX, Xie WY, Ying C, Fen W, Cheng XY, Mao CJ, Liu JY, Liu CF (June 2025). "Butyrate improves abnormal sleep architecture in a Parkinson's disease mouse model via BDNF/TrkB signaling". npj Parkinsons Dis. 11 (1) 175. doi:10.1038/s41531-025-01029-5. PMC   12179271 . PMID   40537481. Prior research suggested that tributyrin, a precursor to butyrate, could enhance NREM sleep. Replicating this experiment, we confirmed the effect (Supplementary Fig. 3A). We observed that tributyrin significantly increased the duration of NREM sleep and decreased time spent in wakefulness during the initial six hours of the dark phase, followed by a decrease in NREM sleep during the subsequent six hours (Supplementary Fig. 3B, C). It may be a self-compensatory sleep mechanism.
  31. ↑ Duan WX, Xie WY, Ying C, Fen W, Cheng XY, Mao CJ, Liu JY, Liu CF (June 2025). "Butyrate improves abnormal sleep architecture in a Parkinson's disease mouse model via BDNF/TrkB signaling". npj Parkinsons Dis. 11 (1) 175. doi:10.1038/s41531-025-01029-5. PMC   12179271 . PMID   40537481.
  32. ↑ Egorin MJ, Yuan ZM, Sentz DL, Plaisance K, Eiseman JL (1999). "Plasma pharmacokinetics of butyrate after intravenous administration of sodium butyrate or oral administration of tributyrin or sodium butyrate to mice and rats". Cancer Chemother Pharmacol. 43 (6): 445–453. doi:10.1007/s002800050922. PMID   10321503.
  33. ↑ Yuan Z, Eiseman J, Plasance K, Sentz D, Bigora S, Fossler M, Young D, Egorin M (1994). "Plasma pharmacokinetics (PK) of butyrate after the administration of tributyrin and Na butyrate to mice and rats". Proc Am Assoc Cancer Res. 35: 429.
  34. ↑ Miyoshi M, Sakaki H, Usami M, Iizuka N, Shuno K, Aoyama M, Usami Y (April 2011). "Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats". Clin Nutr. 30 (2): 252–258. doi:10.1016/j.clnu.2010.09.012. PMID   21051124.
  35. ↑ Su J, He L, Zhang N, Ho PC (January 2006). "Evaluation of tributyrin lipid emulsion with affinity to low-density lipoprotein: pharmacokinetics in adult male Wistar rats and cellular activity on Caco-2 and HepG2 cell lines". J Pharmacol Exp Ther. 316 (1): 62–70. doi:10.1124/jpet.105.090464. PMID   16188956.
  36. ↑ Dosz, Edward; Conley, Devin; Lelah, Michael (2025). "A Novel Butyrate Generator Helps Modulate the Gut-Brain Axis: A Randomized Double-Blind Placebo-Controlled Clinical Study". Nutrition and Dietary Supplements. 17: 127–143. doi: 10.2147/NDS.S565532 . ISSN   1179-1489.
  37. ↑ "ButyraGen™, Short Chain Fatty Acids and Gut Microbiome (BG)". ClinicalTrials.gov. Retrieved 7 July 2026.
  38. ↑ Pérez, José L.; Pulido, Angeles; Pantozzi, Florencia; Martin, Rogelio (October 1990). "Butyrate esterase (4-methylumbelliferyl butyrate) spot test, a simple method for immediate identification of Moraxella (Branhamella) catarrhalis corrected". Journal of Clinical Microbiology . 28 (10). Washington, DC: American Society for Microbiology: 2347–2348. doi:10.1128/jcm.28.10.2347-2348.1990. ISSN   1098-660X. PMC   268174 . PMID   2121784.
  39. ↑ "Tributyrin". AdisInsight. 23 September 2021. Retrieved 3 July 2026.
  40. 1 2 3 Roytman, Stiven; Carli, Giulia; Bohnen, Jeff; Vangel, Robert; Brown, Taylor; Scott, Peter; Albin, Roger; Kanel, Prabesh; Bohnen, Nicolaas (1 June 2024). "Tributyrin Supplementation Increases Brain Butyrate Availability and Improves Parkinson's Disease Motor Symptoms". Journal of Nuclear Medicine. 65 (supplement 2). Society of Nuclear Medicine: 242483. ISSN   0161-5505 . Retrieved 7 July 2026.
  41. 1 2 "Phase 2 Trial of Tributyrin in People With Parkinson's Disease and Cognitive Impairments (BUTTER2)". ClinicalTrials.gov. Retrieved 7 July 2026.
  42. 1 2 3 Herpen, Robert (16 May 2023). "Tributyrin linked to improved motor symptoms, inflammatory markers in Parkinson's". Daily Medical News. Retrieved 7 July 2026.
  43. ↑ Ratajczyk K, Kaczorowska E, Wyka K, Tarasiuk-Zawadzka A, Fichna J, Gajos A (April 2026). "Gut-Brain Signaling in Parkinson's Disease: A Narrative Review". Int J Mol Sci. 27 (8): 3531. doi: 10.3390/ijms27083531 . PMC   13116392 . PMID   42074174. Bohnen JLB et al. [207] assessed the safety and potential biomechanistic effects of tributyrin (a prodrug of butyrate) in an open-label clinical trial. Fourteen PD patients and three control subjects completed a 30-day (±7 days) intervention consisting of dietary supplementation with tributyrin (500 mg taken orally three times daily), demonstrating a satisfactory safety profile and high compliance. Nine patients completed a PET scan with [11C] butyrate before and after the intervention, which allowed for the assessment of treatment-related changes in butyrate uptake by the brain, liver, heart, and gastrointestinal tract, confirming involvement in the target process, i.e., changes in butyrate availability in individual organs and systemic anti-inflammatory effects, as well as improved cognitive and motor functions.
  44. ↑ Banasiewicz T, Domagalska D, Borycka-Kiciak K, Rydzewska G (2020). "Determination of butyric acid dosage based on clinical and experimental studies - a literature review". Prz Gastroenterol. 15 (2): 119–125. doi:10.5114/pg.2020.95556. PMC   7294979 . PMID   32550943.
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