Triacetyluridine is a convenient way of supplementing uridine with clinical evidence for its ameliorative effects on depression, bipolar disorder, subjective mood and well-being, neuroinflammation, and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Here we’ll examine its properties, mechanisms, effects, benefits, dosage, and supplement options.
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In a hurry? Here are the highlights:
- Triacetyluridine is a convenient, bioavailable vehicle for supplementing uridine.
- Triacetyluridine is also known as TAU, uridine triacetate, and PN401 (prescription drugs Vistogard and Xuriden)
- Triacetyluridine is more bioavailable than uridine monophosphate.
- Triacetyluridine per se has clinical evidence of having anti-inflammatory, antineurodegenerative, antidepressant, and cytoprotective effects.
Triacetyluridine Supplement Suggestions:
– Triacetyluridine capsules from Nootropics Depot on their website here.
– Triacetyluridine powder from Nootropics Depot on their website here.
Contents
What is Triacetyluridine?
Triacetyluridine is a prodrug for uridine, meaning it converts to uridine in the body. Specifically, it converts to uridine triphosphate, and “delivers 4- to 6-fold more uridine into systemic circulation than equimolar doses of uridine alone.”1
Triacetyluridine is also referred to as TAU, uridine triacetate. Its formal name is PN401, which refers specifically to the prescription drugs Vistogard and Xuriden, which are used clinically for the emergency treatment of fluorouracil or capecitabine overdose or toxicity following cessation and for hereditary orotic aciduria. They received FDA approval in 20151.
Triacetyluridine Benefits
The current research that has specifically used triacetyluridine shows that it may:
- Alleviate symptoms of depression and bipolar disorder2,3.
- Promote a greater sense of subjective mood and well-being2,3.
- Help attenuate neurodegeneration in cases of Alzheimer’s, Huntington’s, and Parkinson’s diseases4,5.
- Ameliorate cases of pulmonary fibrosis6.
This doesn’t take into account the benefits specifically seen from uridine monophosphate per se, which may include synaptogenesis, cognitive support, catecholamine synthesis, augmenting phospholipid metabolism, greater neuroplasticity, dopamine upregulation, improved mental fluidity, and improved memory, among other things7–13.
Triacetyluridine Effects and Mechanisms – How Does It Work?
In instances of 5‐fluorouracil (5-FU) overdoses or toxicity, oral administration of uridine triacetate within 96 hours rapidly reverses acute cardiotoxicity and neurotoxicity by competing with 5-FU metabolites14.
In cases of hereditary orotic aciduria (uridine monophosphate synthase deficiency), patients’ symptoms are caused by a general uridine deficiency, so triacetyluridine is able to effectively make more uridine available14.
For the purposes of everyday supplementation by average nootropics users, triacetyluridine is simply an effective way of increasing systemic uridine, which has evidence of enhancing dopamine levels and cognition and alleviating symptoms of depression and bipolar disorder via modulating striatal D-2 dopamine receptors2,7–13,15,16.
Triacetyluridine vs. Uridine Monophosphate
Triacetyluridine is essentially just a more potent, more bioavailable form of uridine than uridine monophosphate. Either should produce the aforementioned effects, though the studies cited have used different forms.
See dosage information for both forms below.
Triacetyluridine Dosage
Triacetyluridine dosage for everyday nootropics users is typically 25mg 1-2 times daily.
Uridine monophosphate dosage for everyday nootropics users is typically 250mg 1-2 times daily.
No difference in systemic exposure was seen in fed vs. fasted states, meaning triacetyluridine can be taken with food or on an empty stomach1.
Triacetyluridine Half-Life
The half-life of triacetyluridine itself is about 2 hours. Peak plasma concentration of uridine occurs between 2 and 3 hours after oral administration of triacetyluridine1.
Triacetyluridine Side Effects
Triacetyluridine is generally well-tolerated. Uridine itself is actually found in human mother’s milk and beer17,18, is included in most infant formulas, and is a natural substance in human cells19. As such, side effects of uridine supplementation are rare at normal dosages.
A small percentage of people have reportedly experienced dose-limiting side effects such as vomiting, nausea, and diarrhea, but these were seen with extremely high doses of triacetyluridine used to treat fluorouracil toxicity14. Those high dosages likely aren’t relevant to the type of everyday usage discussed here.
Triacetyluridine Supplements
Triacetyluridine supplements can be found in powder or capsule form from Nootropics Depot on their website.
Triacetyluridine Powder
Buy triacetyluridine powder from Nootropics Depot here.
Triacetyluridine Capsules
You can find triacetyluridine capsules from Nootropics Depot here.
Triacetyluridine Stacks
Triacetyluridine should stack well with things like racetams and ALCAR. Many seasoned nootropics users are likely wanting to employ the famous “Mr. Happy Stack” – uridine, choline, and EPA/DHA (fish oil) – for improved mood, energy, motivation, and synaptogenesis and neurite growth. That’s my morning stack with a raw egg as the choline source.
References
- 1.Cada DJ, Mbogu U, Bindler RJ, Baker DE. Uridine Triacetate. Hospital Pharmacy. June 2016:484-488. doi:10.1310/hpj5106-484
- 2.Kondo DG, Sung Y-H, Hellem TL, et al. Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder. Journal of Child and Adolescent Psychopharmacology. April 2011:171-175. doi:10.1089/cap.2010.0054
- 3.de Sousa RT, Machado-Vieira R, Zarate CA Jr, Manji HK. Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder. Expert Opinion on Therapeutic Targets. July 2014:1131-1147. doi:10.1517/14728222.2014.940893
- 4.Saydoff J, Liu LS, Hu Z, von Borstel RW. P1-404 Uridine prodrug PN401 has beneficial effects in models of Alzheimer’s disease, hypoxia and oxidative stress. Neurobiology of Aging. July 2004:S213. doi:10.1016/s0197-4580(04)80716-4
- 5.Saydoff J, Sheng JG, Hu Z, et al. [P-188]: PN401 decreases neurodegeneration in models of Alzheimer’s, Huntington’s and Parkinson’s disease, neuroinflammation, excitotoxicity and has antiepileptic activity. Alzheimer’s & Dementia. July 2005:S68-S68. doi:10.1016/j.jalz.2005.06.247
- 6.Cicko S, Grimm M, Ayata K, et al. Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis. Respir Res. September 2015. doi:10.1186/s12931-015-0264-9
- 7.Myers CS, Fisher H, Wagner GC. Uridine reduces rotation induced by l-Dopa and methamphetamine in 6-OHDA-treated rats. Pharmacology Biochemistry and Behavior. December 1995:749-753. doi:10.1016/0091-3057(95)00169-w
- 8.Myers CS, Napolitano M, Fisher H, Wagner GC. Uridine and Stimulant-Induced Motor Activity. Experimental Biology and Medicine. October 1993:49-53. doi:10.3181/00379727-204-43633
- 9.AGNATI L, FUXE K, RUGGERI M, et al. Effects of chronic treatment with uridine on striatal dopamine release and dopamine related behaviours in the absence or the presence of chronic treatment with haloperidol. Neurochemistry International. 1989:107-113. doi:10.1016/0197-0186(89)90082-x
- 10.FARABEGOLI C, PICH EM, CIMINO M, AGNATI LF, FUXE K. Chronic uridine treatment reduces the level of [3H]spiperone-labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours. Acta Physiologica Scandinavica. February 1988:209-216. doi:10.1111/j.1748-1716.1988.tb08319.x
- 11.Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary Uridine-5’-Monophosphate Supplementation Increases Potassium-Evoked Dopamine Release and Promotes Neurite Outgrowth in Aged Rats. JMN. 2005:137-146. doi:10.1385/jmn:27:1:137
- 12.Wurtman RJ, Cansev M, Ulus IH. Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J Nutr Health Aging. March 2009:189-197. doi:10.1007/s12603-009-0056-3
- 13.Cansev M. Uridine and cytidine in the brain: Their transport and utilization. Brain Research Reviews. September 2006:389-397. doi:10.1016/j.brainresrev.2006.05.001
- 14.Ma WW, Saif MW, El-Rayes BF, et al. Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. Cancer. September 2016:345-356. doi:10.1002/cncr.30321
- 15.Klivenyi P, Gardian G, Calingasan NY, et al. Neuroprotective Effects of Oral Administration of Triacetyluridine Against MPTP Neurotoxicity. NMM. 2004:087-092. doi:10.1385/nmm:6:2-3:087
- 16.Jensen JE, Daniels M, Haws C, et al. Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Experimental and Clinical Psychopharmacology. 2008:199-206. doi:10.1037/1064-1297.16.3.199
- 17.SUGAWARA M, SATO N, NAKANO T, IDOTA T, NAKAJIMA I. Profile of Nucleotides and Nucleosides of Human Milk. Journal of Nutritional Science and Vitaminology, J Nutr Sci Vitaminol. 1995:409-418. doi:10.3177/jnsv.41.409
- 18.Yamamoto T, Moriwaki Y, Takahashi S, et al. Effect of beer on the plasma concentrations of uridine and purine bases. Metabolism. October 2002:1317-1323. doi:10.1053/meta.2002.34041
- 19.Wurtman RJ. Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metabolism. October 2008:S6-S10. doi:10.1016/j.metabol.2008.07.007
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