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Triacetyluridine – The Ultimate Guide – Benefits, Dosage, & More

Last Updated: August 21, 2021 4 Comments – 5 min. read

Medically reviewed by Jessica Pyhtila, PharmD, BCGP, BCPS.

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.

Disclosure:  Some of the links on this page are referral links. At no additional cost to you, if you choose to make a purchase after clicking through those links, I will receive a small commission. This allows me to continue producing high-quality, ad-free content on this site and pays for the occasional cup of coffee. I have first-hand experience with every product or service I recommend, and I recommend them because I genuinely believe they are useful, not because of the commission I get if you decide to purchase through my links. Read more here.

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.

Contents

  • What is Triacetyluridine?
  • Triacetyluridine Benefits
  • Triacetyluridine Effects and Mechanisms – How Does It Work?
  • Triacetyluridine vs. Uridine Monophosphate
  • Triacetyluridine Dosage
  • Triacetyluridine Half-Life
  • Triacetyluridine Side Effects
  • Triacetyluridine Stacks

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​ Uridine is a nucleotide with many neurological properties.

Triacetyluridine is also referred to as TAU, uridine triacetate. The FDA-approved version is sometimes called 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 2015​1​.

Triacetyluridine Benefits

The current research that has specifically used triacetyluridine shows that it may:

  • Alleviate symptoms of depression and bipolar disorder​2,3​.
  • Promote a greater sense of subjective mood and well-being​2,3​.
  • Help attenuate neurodegeneration in cases of Alzheimer’s, Huntington’s, and Parkinson’s diseases​4,5​.
  • Ameliorate cases of pulmonary fibrosis​6​.

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 things​7–13​.

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 metabolites​14​.

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 available​14​. Uridine is also applicable for Parkinson’s Disease and Huntington’s Disease by preventing the loss of dopamine-producing neurons​15​.

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 receptors​2,7–13,16,17​.

neurons

Triacetyluridine vs. Uridine Monophosphate

Triacetyluridine is essentially just a more potent, more bioavailable form of uridine than uridine monophosphate. It converts to uridine in the body. 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. This higher dosage is again due to the comparatively lower bioavailability of uridine monophosphate compared to triacetyluridine.

No difference in systemic exposure was seen in fed vs. fasted states, meaning triacetyluridine can be taken with food or on an empty stomach​1​.

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 triacetyluridine​1​.

Triacetyluridine Side Effects

Triacetyluridine is generally well-tolerated. Uridine itself is actually found in human mother’s milk and beer​18,19​, is included in most infant formulas, and is a natural substance in human cells​20​. 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 toxicity​14​. Those high dosages likely aren’t relevant to the type of everyday usage discussed 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. 1.
    Cada DJ, Mbogu U, Bindler RJ, Baker DE. Uridine Triacetate. Hospital Pharmacy. Published online June 2016:484-488. doi:10.1310/hpj5106-484
  2. 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. Published online April 2011:171-175. doi:10.1089/cap.2010.0054
  3. 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. Published online July 24, 2014:1131-1147. doi:10.1517/14728222.2014.940893
  4. 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. Published online July 2004:S213. doi:10.1016/s0197-4580(04)80716-4
  5. 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. Published online July 2005:S68-S68. doi:10.1016/j.jalz.2005.06.247
  6. 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. Published online September 15, 2015. doi:10.1186/s12931-015-0264-9
  7. 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. Published online December 1995:749-753. doi:10.1016/0091-3057(95)00169-w
  8. 8.
    Myers CS, Napolitano M, Fisher H, Wagner GC. Uridine and Stimulant-Induced Motor Activity. Experimental Biology and Medicine. Published online October 1, 1993:49-53. doi:10.3181/00379727-204-43633
  9. 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. Published online 1989:107-113. doi:10.1016/0197-0186(89)90082-x
  10. 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. Published online February 1988:209-216. doi:10.1111/j.1748-1716.1988.tb08319.x
  11. 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. Published online 2005:137-146. doi:10.1385/jmn:27:1:137
  12. 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. Published online March 2009:189-197. doi:10.1007/s12603-009-0056-3
  13. 13.
    Cansev M. Uridine and cytidine in the brain: Their transport and utilization. Brain Research Reviews. Published online September 2006:389-397. doi:10.1016/j.brainresrev.2006.05.001
  14. 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. Published online September 13, 2016:345-356. doi:10.1002/cncr.30321
  15. 15.
    Klivenyi P, Gardian G, Calingasan N, et al. Neuroprotective effects of oral administration of triacetyluridine against MPTP neurotoxicity. Neuromolecular Med. 2004;6(2-3):87-92. doi:10.1385/NMM:6:2-3:087
  16. 16.
    Klivenyi P, Gardian G, Calingasan NY, et al. Neuroprotective Effects of Oral Administration of Triacetyluridine Against MPTP Neurotoxicity. NMM. Published online 2004:087-092. doi:10.1385/nmm:6:2-3:087
  17. 17.
    Jensen JE, Daniels M, Haws C, et al. Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Experimental and Clinical Psychopharmacology. Published online 2008:199-206. doi:10.1037/1064-1297.16.3.199
  18. 18.
    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. Published online 1995:409-418. doi:10.3177/jnsv.41.409
  19. 19.
    Yamamoto T, Moriwaki Y, Takahashi S, et al. Effect of beer on the plasma concentrations of uridine and purine bases. Metabolism. Published online October 2002:1317-1323. doi:10.1053/meta.2002.34041
  20. 20.
    Wurtman RJ. Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metabolism. Published online October 2008:S6-S10. doi:10.1016/j.metabol.2008.07.007

Medical Disclaimer:  While I love diving into and extracting useful information from clinical research related to health, fitness, supplements, and more, I am in no way a medical expert. The content on this website is for informational purposes only; it is not professional medical advice, nor is it a substitute for professional medical advice. None of the statements on this website have been evaluated by the FDA. Products mentioned are not intended to diagnose, treat, cure, or prevent any disease. Read my lengthier medical disclaimer here.

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About John Williamson

Analytical and entrepreneurial-minded data nerd, usability enthusiast, armchair research scientist, health/nutrition/supplement aficionado, and Oxford comma advocate. I lead the Paid Search marketing efforts at Gild Group. I'm not a big fan of social media, but you can find me on LinkedIn and Reddit.

Reader Interactions

Comments

  1. Nathan says

    July 9, 2021 at 12:31 pm

    Do you need to take triacetyluridine that often (4-6 hours) to get a benefit?

    Reply
  2. Dr Bob Daugherty ND says

    June 4, 2021 at 11:45 am

    John, I just discovered your blog and really like and appreciate your reviews. They are most clear and well researched, my strong compliments!

    I as a 74yr old ancient ager I hope you would write something on these two “topics” too:

    1. Best supplements/noots for oldies and for their brain health too.

    2. Best supplements/noots for physical coordination. I have a balance disorder from a severe ear injury and keep searching for something that would help. I have a pristine diet, work out, mediate, have tried quite a few things but nothing has helped so far.

    I sure wish you every success, and I will keep spreading the word too, dr. b

    Reply
    • John Williamson says

      June 12, 2021 at 4:10 pm

      Thanks for the suggestions and for the kind words!

      Reply
      • Tim says

        April 9, 2022 at 7:03 pm

        John,

        Your comments are informative and concise – thanks!

        I’m an older guy interested in stacks that support positive moods and high focus. I also want something that doesn’t require increasing the dosage to work. I’m healthy and exercise daily, so no worries there. Would you suggest ‘Happy Stack’?

        Reply

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