Uridine: Benefits, Uridine Monophosphate Dosage, Safety And Research

ByJustin Updated on

Uridine is a nucleoside, one of the building blocks of RNA, that the brain also uses to make phosphatidylcholine, a key component of nerve-cell membranes and synapses. As a supplement it is usually sold as uridine monophosphate (UMP). Its best human evidence comes from Souvenaid, a medical drink that combines 625 mg of UMP with DHA, choline and vitamins, which produced small memory benefits in very early Alzheimer’s disease but not in more advanced disease. Claims that uridine lifts mood rest mostly on animal research.

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Key Takeaways

  • Uridine supplies the brain with the building blocks it uses, along with choline and DHA, to make phosphatidylcholine through the Kennedy pathway.
  • Nearly all human evidence comes from the multi-nutrient product Souvenaid (Fortasyn Connect), so effects cannot be pinned on uridine alone.
  • Souvenaid modestly improved memory scores in very mild Alzheimer’s disease, failed in mild-to-moderate disease, and showed slower decline on secondary outcomes in prodromal Alzheimer’s.
  • Antidepressant claims are preliminary and based mainly on rat studies.
  • Citicoline is a backdoor uridine source: its cytidine portion is converted to uridine in humans.
  • Souvenaid was well tolerated in trials up to three years, with adverse events similar to control.

What Is Uridine?

Uridine is a pyrimidine nucleoside made of the base uracil attached to a ribose sugar. Your body makes it and recycles it constantly, and in humans it appears to be the only pyrimidine nucleoside circulating in the blood. According to work by MIT neuroscientist Richard Wurtman, most of the CTP the human brain uses to make phosphatidylcholine comes from circulating uridine.[1]

What Is Uridine Monophosphate?

Uridine monophosphate (UMP), also called uridine 5′-monophosphate, is uridine with a phosphate group attached. It is the form found in breast milk and infant formula, and the form used in Souvenaid.[1][7] Most supplements sell it as uridine 5′-monophosphate disodium salt, a stable, water-soluble powder.

How Uridine Works: The Kennedy Pathway

Phosphatidylcholine is made through the Kennedy pathway (also called the CDP-choline pathway) in three main steps:[1]

  1. Choline is converted to phosphocholine.
  2. Phosphocholine plus CTP forms CDP-choline (citicoline). Uridine is the main source of this CTP: it is converted to UTP and then CTP.
  3. CDP-choline plus diacylglycerol, which can carry omega-3 DHA, forms phosphatidylcholine.

Because each step depends on the supply of its ingredients, Wurtman’s group proposed that giving all three precursors together (uridine, choline and DHA) could increase membrane and synapse formation. In gerbils, DHA alone increased the number of dendritic spines in the hippocampus, and the effect roughly doubled when the animals also received UMP. The combination also improved maze performance in rodents.[1] Those animal findings led to Souvenaid. Note that Wurtman’s institution holds patents on these nutrient combinations licensed to Souvenaid’s maker, and he advised the company.[1]

Uridine Benefits: What The Research Shows

Memory In Early Alzheimer’s Disease (Evidence: Moderate For The Combination, Limited For Uridine Alone)

Souvenaid’s active blend, Fortasyn Connect, supplies 625 mg of UMP, 1,200 mg of DHA plus EPA, 400 mg of choline, phospholipids, B vitamins, vitamins C and E and selenium each day.[7] Its trials tell a consistent story: small benefits early, none later.

Trial Population Duration Main Result
Souvenir II (Scheltens 2012) 259 people with very mild to mild Alzheimer’s 24 weeks Small memory improvement (Cohen’s d 0.21)[2][7]
S-Connect (Shah 2013) 527 people with mild-to-moderate Alzheimer’s on medication 24 weeks No benefit on ADAS-cog, function or global measures[3][7]
LipiDiDiet (Soininen 2017) 382 people with prodromal Alzheimer’s 24 months Primary memory endpoint not met; 45% less worsening on CDR-SB and 26% less hippocampal atrophy[4][7]
LipiDiDiet extension (Soininen 2021) Prodromal Alzheimer’s 36 months Larger differences on cognitive and atrophy measures; dementia diagnoses similar (43.1% vs 44.3%)[5][7]

Independent reviewers are more skeptical than the trial sponsors. A 2017 systematic review concluded that Souvenaid had failed to significantly slow cognitive decline, though it appeared to cause minor improvements in verbal memory in some people with very early disease.[6] The LipiDiDiet trial was likely underpowered for its primary endpoint, and its positive findings were on secondary outcomes.[7]

Two caveats matter for nootropic users. First, these trials tested a full nutrient package, not uridine on its own, so we cannot say how much of the effect (if any) comes from UMP. Second, the benefit appeared only in people with early brain changes. It is unclear whether people who already eat a diet rich in these nutrients would benefit at all.[7]

Memory And Focus In Healthy Adults (Evidence: Not Studied)

We found no randomized controlled trials of uridine monophosphate alone for memory, focus or learning in healthy adults. Popular “uridine stacks” are built on the Kennedy-pathway theory and animal data, not on human results.

Uridine For Depression And Mood (Evidence: Preliminary, Mostly Animal)

Interest in uridine for depression traces largely to a 2005 rat study, in which uridine and omega-3 fatty acids each showed antidepressant-like effects, and the combination produced stronger, faster effects than either alone.[8] Rodent behavioral tests do not reliably predict effects in people. We could not verify any adequately controlled human trials showing that uridine improves depression or bipolar disorder, so it should not be used in place of treatment. If you have a mood disorder, talk with your psychiatrist before trying it.

Uridine Sources: Foods, Citicoline And Supplements

Uridine Foods

Many foods contain RNA and therefore uridine, but that does not mean they raise blood uridine levels. Wurtman noted that no uridine-containing adult food has ever been compellingly shown to raise plasma uridine in humans, and early animal work suggested the liver breaks down most uridine absorbed from the gut.[1] Breast milk is the clear exception: it provides substantial bioavailable uridine to infants as UMP.[1] One study found that beer raised plasma uridine about 1.8-fold within 30 minutes, which is a curiosity rather than a recommendation.[9]

Citicoline Yields Uridine

When you take citicoline (CDP-choline), it is broken down in the gut into choline and cytidine, and in humans the cytidine is converted into uridine.[10] In other words, citicoline delivers both halves of the Kennedy pathway’s starting materials. That is one reason many people use citicoline instead of stacking separate choline and uridine products. Our Alpha-GPC vs citicoline comparison covers the differences.

Triacetyluridine (Uridine Triacetate)

Triacetyluridine, also called uridine triacetate or TAU, is an acetylated prodrug of uridine. It is the active ingredient of two FDA-approved prescription drugs: Xuriden, for the rare inherited disorder hereditary orotic aciduria, and Vistogard, an emergency treatment after overdose of the chemotherapy drugs fluorouracil (5-FU) or capecitabine.[11][12] Some nootropic vendors sell triacetyluridine as a “more potent” uridine, but there are no published trials of it as a cognitive supplement, and it is a drug ingredient we do not recommend self-dosing.

Uridine Dosage: Studied Doses

Purpose Dose Duration Study
Early Alzheimer’s (as part of Souvenaid) 625 mg UMP daily, with DHA, EPA, choline and vitamins 24 weeks to 36 months Souvenir II; LipiDiDiet[2][4]
Hereditary orotic aciduria (prescription) Uridine triacetate 60–120 mg/kg daily Long term Xuriden label[11]

There is no established uridine monophosphate dosage for cognition in healthy people. The best-studied intake is the 625 mg of UMP per day used in Souvenaid, always alongside DHA and choline. Supplement labels vary widely, so compare the amount of UMP per serving rather than capsule count, and remember that the disodium salt weighs more than uridine itself.

Uridine Side Effects And Safety

In Souvenaid trials, compliance was above 90%, gastrointestinal complaints were the most common events judged possibly related to the product, and there were no clinically relevant changes in lab values or vital signs. Pooled data showed no increase in adverse events (odds ratio 0.84) or serious adverse events (odds ratio 0.95) compared with an isocaloric control drink, and three-year data suggested continued tolerability.[7] In the small trial behind the prescription uridine triacetate product Xuriden, no adverse reactions were reported.[11]

What we do not know:

  • The long-term safety of uridine monophosphate taken alone, especially at doses above 625 mg a day.
  • Whether uridine is safe for people with bipolar disorder or other mood disorders.
  • Its safety in pregnancy and breastfeeding as a supplement.

Drug Interactions And Who Should Avoid Uridine

  • Fluoropyrimidine chemotherapy: Uridine triacetate is used as an antidote for 5-FU and capecitabine overdose.[12] If you are receiving these drugs, do not take any uridine supplement without your oncologist’s approval, since it could interfere with treatment.
  • Mood disorders and psychiatric medication: Because uridine is promoted for mood but lacks human safety data in these groups, check with your prescriber first.
  • Multiple vitamin-containing products: Souvenaid contains B vitamins, vitamin E and selenium, so avoid stacking it with high-dose supplements of the same nutrients.[7]

How Uridine Stacks With Choline And Omega-3s

The logic of a uridine stack comes straight from the Kennedy pathway: uridine plus a choline source plus DHA. That mirrors Souvenaid’s formula, which is the only version of the stack with clinical data.[1]

Mind Lab Pro: Citicoline Instead Of Separate Uridine

Mind Lab Pro does not contain uridine monophosphate, but it provides 250 mg of citicoline (Cognizin), which the body splits into choline and cytidine, a uridine precursor. It also contains 100 mg of phosphatidylserine, below the 300 mg used in most PS trials, plus Bacopa, lion’s mane, L-theanine and other ingredients. It is not a substitute for the 625 mg of UMP used in Souvenaid, but it is a reasonable, well-tolerated daily stack. Read our Mind Lab Pro review.

Check Mind Lab Pro Price

Where To Buy Uridine Monophosphate

If you want to try UMP on its own, choose a single-ingredient product that states the UMP content per serving and is third-party tested. We generally recommend Nootropics Depot for standardized single ingredients. On Amazon, buy only from listings marked “Sold by Nootropics Depot.”

Check Nootropics Depot Uridine Monophosphate

For more evidence-ranked options, see our list of the best supplements for memory or browse the full ingredient library.

Uridine FAQs

What Is Uridine Monophosphate Used For?

Uridine monophosphate is used as a precursor for brain phosphatidylcholine synthesis. Its main clinical use has been as part of Souvenaid for early Alzheimer’s disease, where effects were small and limited to early stages.[6][7]

What Are The Benefits Of Uridine?

The best-supported benefit is a modest memory effect in very early Alzheimer’s disease when uridine is combined with DHA and choline.[2] Benefits for healthy people and for mood have not been shown in human trials.

Should I Take Uridine And Choline Together?

If you take uridine, pairing it with choline and DHA follows the only formula tested in humans.[1] Citicoline alone covers choline and part of the uridine side.[10]

Does Uridine Help Depression?

The evidence is preliminary and mostly from rats.[8] Do not use uridine instead of proven depression treatment.

Is Triacetyluridine Better Than Uridine Monophosphate?

Triacetyluridine is a prodrug used in FDA-approved prescription medicines, not a studied nootropic.[12] There is no human evidence that it improves cognition, so “better” is unproven.

What Foods Are High In Uridine?

Breast milk is the main food source with proven bioavailable uridine. In adults, no food has been convincingly shown to raise blood uridine levels.[1]

Medical disclaimer: This article is for educational purposes only and is not medical advice. Dietary supplements are not evaluated by the FDA to diagnose, treat, cure or prevent any disease. Talk with your doctor or pharmacist before starting a supplement, especially if you are pregnant, nursing, take prescription medication or have a medical condition. Read our full medical disclaimer.

References

  1. Wurtman RJ. A nutrient combination that can affect synapse formation. Nutrients. 2014;6(4):1701-1710. DOI
  2. Scheltens P, et al. Efficacy of Souvenaid in mild Alzheimer’s disease: results from a randomized, controlled trial (Souvenir II). Journal of Alzheimer’s Disease. 2012;31:225-236. PubMed
  3. Shah RC, et al. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer’s disease. Alzheimer’s Research & Therapy. 2013;5:59. PMC
  4. Soininen H, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer’s disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurology. 2017;16:965-975. PMC
  5. Soininen H, et al. 36-month LipiDiDiet multinutrient clinical trial in prodromal Alzheimer’s disease. Alzheimer’s & Dementia. 2021;17:29-40. PMC
  6. Onakpoya IJ, Heneghan CJ. The efficacy of supplementation with the novel medical food, Souvenaid, in patients with Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. Nutritional Neuroscience. 2017;20(4):219-227. PubMed
  7. Alzheimer’s Drug Discovery Foundation. Souvenaid (supplement). Cognitive Vitality report. ADDF Cognitive Vitality
  8. Carlezon WA, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biological Psychiatry. 2005;57(4):343-350. PubMed
  9. Yamamoto T, et al. Effect of beer on the plasma concentrations of uridine and purine bases. Metabolism. 2002;51(10):1317-1323. PubMed
  10. Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochemical Pharmacology. 2000;60(7):989-992. PubMed
  11. U.S. National Library of Medicine, DailyMed. XURIDEN (uridine triacetate) oral granules, prescribing information. DailyMed
  12. Ison G, et al. FDA approval: uridine triacetate for the treatment of patients following fluorouracil or capecitabine overdose… Clinical Cancer Research. 2016;22(18):4545-4549. PubMed

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