Glyceryl-tris-3-hydroxybutyrate

Glyceryl-tris-3-hydroxybutyrate
Names
IUPAC name
2,3-bis(3-hydroxybutanoyloxy)propyl 3-hydroxybutanoate
Other names
Triacylglycerol of 3-hydroxybutyrate; Glyceryl tris (3-hydroxybutyrate); Glycerol-tri-3-hydroxybutyrate; Tris(3-hydroxybutyrin) glyceride; 3GHB; G3HB; Neuridan; TriKeto 3BHB; 3BHB
Identifiers
3D model (JSmol)
  • InChI=1S/C15H26O9/c1-9(16)4-13(19)22-7-12(24-15(21)6-11(3)18)8-23-14(20)5-10(2)17/h9-12,16-18H,4-8H2,1-3H3
    Key: NHEUWFPWBFBDRF-UHFFFAOYSA-N
  • CC(CC(=O)OCC(COC(=O)CC(C)O)OC(=O)CC(C)O)O
Properties
C15H26O9
Molar mass 350.364 g·mol−1
Pharmacology
Drug class Triglyceride; Ketone ester; Histone deacetylase inhibitor
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Glyceryl-tris-3-hydroxybutyrate (3GHB), sold under brand names like Neuridan and TriKeto 3BHB, is a triglyceride and ketone ester and the glycerol triester of the short-chain fatty acid and ketone body β-hydroxybutyric acid (β-hydroxybutyrate; BHB; 3-hydroxybutyrate).[1][2][3][4][5][6][7] It is slowly metabolized and converted into BHB in the body.[2][8][1][4][5][9] Ketone esters like 3GHB can induce rapid, significant, and sustained ketosis with oral administration and are an alternative to the ketogenic diet and fasting for achieving ketosis.[1][2][10][8][9] They are able to overcome the pharmacokinetic limitations of exogenous ketone bodies, such as BHB's extremely rapid metabolism and short elimination half-life.[9]

3GHB is a water-soluble triglyceride and has been investigated for potential use in parenteral nutrition.[4][5] It shows dose-dependent neuroprotective effects against MPTP-induced dopaminergic neurotoxicity in rodents.[1][9] It was suggested that this might be mediated by histone deacetylase (HDAC) inhibition.[1][9] There has been interest in 3GHB in the potential treatment of neurological conditions such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury.[3][1][9][8][7] 3GHB has been patented for various uses.[6][7] The clinical pharmacokinetics of 3GHB are being studied.[11][10]

See also

References

  1. 1 2 3 4 5 6 Hashim SA, VanItallie TB (September 2014). "Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester". J Lipid Res. 55 (9): 1818–1826. doi:10.1194/jlr.R046599. PMC 4617348. PMID 24598140. Recently, oral administration of glyceryl-tris-3-hydroxybutyrate (3GHB), the TG of βHB, was found to exert an extended neuroprotective action against MPTP-induced neuronal destruction in the SNpc of mice. It was shown that 3GHB protects these neurons in a dose-dependent manner (48). The study's authors suggested that this protection might be mediated via inhibition of HDAC. They concluded that this new ketone ester (KE), 3GHB, represented a promising preventive and/or therapeutic strategy for a range of pathological conditions affecting the brain, including PD and AD (48). [...] Two KEs are known to be under current study: a) 1,3-butanediol monoester of βHB (KME) (77, 79, 80, 81, 82, 83, 84) and b) 3GHB (48, 85, 86). Studies have demonstrated that orally or intravenously administered 1,3-butanediol or glycerol esters of βHB are safe and well tolerated in animals (80, 86), and that the orally administered 1,3-butanediol monoester is also safe and well tolerated in humans (79).
  2. 1 2 3 Veyrat-Durebex C, Reynier P, Procaccio V, Hergesheimer R, Corcia P, Andres CR, Blasco H (2018). "How Can a Ketogenic Diet Improve Motor Function?". Front Mol Neurosci. 11 15. doi:10.3389/fnmol.2018.00015. PMC 5790787. PMID 29434537. One therapeutic goal is to replace the KD, and its strict requirements for observance, with dietary supplements that could generate sustained ketosis. KEs are considered to be substitutes for KD and are suitable for oral treatment, compared to KBs. Ingestion of KEs can directly increase blood levels of KBs without the delay observed in KD or fasting (Hashim and VanItallie, 2014). The main KEs used are 1,3-butanediol monoester of βOHB and glyceryl-tri-3-hydroxybutyrate (3GHB) (Brunengraber, 1997). Oral and intravenous administering of KEs demonstrated that they were safe and well-tolerated in animals and humans (Clarke et al., 2012a,b), which makes them an interesting complementary treatment.
  3. 1 2 Poff AM, Rho JM, D'Agostino DP (2019). "Ketone Administration for Seizure Disorders: History and Rationale for Ketone Esters and Metabolic Alternatives". Front Neurosci. 13 1041. doi:10.3389/fnins.2019.01041. PMC 6803688. PMID 31680801. In addition to BD-derived ketone esters, there also exist glycerol-derived ketone esters of BHB. The diol BD and triol glycerol contain two or three hydroxyl groups, respectively, and through transesterification, these functional groups can pair with ketone bodies to make mono-esters, di-esters, or such as in the case of glycerol, a tri-ester compound known as glyceryl-tris-3-hydroxybutyrate (Hashim and VanItallie, 2014).
  4. 1 2 3 Birkhahn RH, McCombs C, Clemens R, Hubbs J (March 1997). "Potential of the monoglyceride and triglyceride of DL-3-hydroxybutyrate for parenteral nutrition: synthesis and preliminary biological testing in the rat". Nutrition. 13 (3): 213–219. doi:10.1016/s0899-9007(96)00404-2. PMID 9131681.
  5. 1 2 3 Brunengraber H (March 1997). "Potential of ketone body esters for parenteral and oral nutrition". Nutrition. 13 (3): 233–235. doi:10.1016/s0899-9007(96)00409-1. PMID 9131688.
  6. 1 2 "Glyceryl 3-hydroxybutyrates for migraine symptom management". Google Patents. 23 December 2016. Retrieved 6 July 2026.
  7. 1 2 3 "Glyceryl 3-hydroxybutyrates for traumatic brain injury". Google Patents. 12 January 2017. Retrieved 6 July 2026.
  8. 1 2 3 Morris G, Puri BK, Carvalho A, Maes M, Berk M, Ruusunen A, Olive L (June 2020). "Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?". Int J Neuropsychopharmacol. 23 (6): 366–384. doi:10.1093/ijnp/pyaa008. PMC 7311648. PMID 32034911. These enduring problems with tolerability and lingering concerns over the development of dyslipidemia in long-term use have led to an increasing research focus on the use of exogenous ketone supplements in the form of KB salts and esters, with common examples being 1, 3-butanediol monoester of BHB and glyceryl-tris-3-hydroxybutyrate, which provide high levels of BHB directly to the body without the need to induce ketogenesis and thus without elevations in free fatty acids and, perhaps more importantly thus far, no evidence of induced dyslipidemia (Hashim and VanItallie, 2014; Veech, 2014).
  9. 1 2 3 4 5 6 J. Blesa, V. Jackson-Lewis, N. Boaz, S. Hashim, S. Przedborski Glyceryl-tris-3-hydroxybutyrate protects dopaminergic neurons in a MPTP model of Parkinson's disease, Society for Neuroscience, New Orleans,LA (2012) (Abstract in 2012 Neuroscience Meeting Planner, Society for Neuroscience. New Orleans, LA, October 17, 2012). https://scholar.google.com/scholar?cluster=6468425617178300327 https://web.archive.org/web/20260706233430/https://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6d23afc2-0250-4ced-9dd4-2b56fb9c00db&cKey=f83dda4e-b240-4f0d-b6d1-0e015d8893aa&mKey=%7B70007181-01C9-4DE9-A0A2-EEBFA14CD9F1%7D "Previously, we have shown that the administration of D-B-Hydroxybutyrate (DBHB) mitigates tyrosine hydroxylase positive (TH+) neuronal loss in the substantia nigra pars compacta of mice caused by mitochondrial poisons such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). [...] One major limitation to the clinical use of DBHB resides with its extremely short half-life, hence, requiring its infusion via Alzet pumps to reach effective steady-state levels in the blood. Because of the short half-life of DBHB, an analogue of the DBHB, Glyceryl-tris-3-hydroxybutyrate (3GHB), was synthesized. This compound has a pharmacokinetic suitability for single-dose daily administration. We, therefore, have tested 3GHB to gauge the effectiveness of its “extended” neuroprotective action, both in in vivo and in vitro studies in comparison to DBHB. We show that 3GHB protects SNpc dopaminergic neurons against MPTP in a dose dependent manner and prevents the development of abnormalities in mice. Also, we have preliminary data suggesting that this protection may be via inhibition of histone deacetylase activity (HDAC). This new analog may represent a promising and valuable therapeuthic strategy for a range of pathological conditions affecting the brain, such as Parkinson’s Disease or Alzheimer’s Disease."
  10. 1 2 Plourde G, Roumes H, Suissa L, Hirt L, Doche É, Pellerin L, Bouzier-Sore AK, Quintard H (July 2024). "Neuroprotective effects of lactate and ketone bodies in acute brain injury". J Cereb Blood Flow Metab. 44 (7): 1078–1088. doi:10.1177/0271678X241245486. PMC 11179615. PMID 38603600. Finally, enteral KB are now available in the form of ketone esters (such as 1,3-butanediol monoester of beta-hydroxybutyrate or glyceryl-tris-3-hydroxybutyrate, two precursors of KB). The compound (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is now considered a safe food supplement for humans by the U.S. Food and Drug Administration. Ketone esters induce a rapid and significant ketosis after a single oral intake and as such, represent an interesting therapeutic avenue in acute care.21,95
  11. ↑ Trial, MedPath (15 July 2025). "Comparison of Pharmacokinetic Responses to..." MedPath Trial. Retrieved 6 July 2026.
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