Uridine Monophosphate As Nootropic: How It Works + Benefits

Written by Andy Mobbs
featured image for article on uridine monophosphate

Uridine Monophosphate is one compound that’s starting to become really popular amongst nootropic lovers. In this article, I’ll share the findings of my research on Uridine Monophosphate – how it works and how it can potentially benefit you. I’ll also recommend a nootropic stack that can help maximize Uridine’s nootropic powers!

What is Uridine Monophosphate?

Uridine is a building block of RNA, which allows the body to make proteins. The hard copy of all of our proteins is kept on DNA in the nucleus of our cells, but DNA never leaves the nucleus.

Because DNA never leaves the nucleus it needs to be copied onto RNA in a process called transcription. The RNA then travels outside the nucleus to ribosomes where the RNA code is translated into sequences of amino acids which make up our proteins.

uridine is a building block of rna

What does Uridine Monophosphate do in the brain?

Uridine is so much more than just RNA. Once absorbed into the body, Uridine Monophosphate can cross the blood-brain barrier, which means it can easily pass into the brain (1, 2).

Once there, it can convert into Uridine Tri Phosphate (UTP), then Cytidine Tri Phosphate (CTP), CDP Choline, and then when combined with Diacylglycerol it turns in Phosphatidylcholine, in a pathway known as the Kennedy Pathway. The pathway is pictured below with the enzymes that catalyze the conversions on the arrows (3).

kennedy pathway

Once we have Phosphatidylcholine, we can produce any of the other 3 main phospholipids which are Sphingomyelin, Phosphatidylserine, and Phosphatidylethanolamine.

uridine monophosphate, phosphatidylcholine
Phosphatidylcholine is used to make the other major phospholipids and acetylcholine.

These molecules are critical for health. Phospholipids form the basis of our cell membranes, meaning they are vital for each of our 20 trillion cells and the vast network of communication that takes place between them throughout our body.

Without phospholipids, nothing can get in or out of cells. Phospholipids are also vital for our neurons to grow, repair, and form new connections or synapses with other neurons.

Acetylcholine is known as the smart neurotransmitter and is involved in creating focus, attention, memory, and motivation. It’s also released from neuromuscular junctions which allows our brains to contract our muscles.

Phosphatidylcholine and Sphingomyelin form the outside layer of our cell membranes, whereas Phosphatidylserine and Phosphatidylethanolamine form the inside layer. Here’s how it looks like:

Diagram of a cell membrane showing all the main phospholipids
Diagram of a cell membrane showing all the main phospholipids, along with cholesterol that is also needed in every cell membrane to provide stability to the phospholipids

Which is more absorbable? Uridine vs Uridine Monophosphate

Uridine Monophosphate is such an important molecule for brain development that its found in significant amounts in breast milk and infant formulas (4). Whilst Uridine is found in a number of foods including beer, fish, and broccoli, it’s mostly made up of the RNA form which is not well absorbed in the gut.

Supplementing with the morehighly absorbed Uridine Monophosphate is a good option for those wanting to increase their uridine levels.

Studies that support Uridine Monophosphate’s absorbability

A study by Cansev et al. found that it took just 30 minutes for rats who were fed food containing Uridine Monophosphate to show increased levels of all phospholipids and acetylcholine in their blood. These increases were also confirmed to be present in their brains that were dissected 8 hours later (5).

A review by Wurtman et al. also found these increases in acetylcholine and brain phospholipids led to an increased number of dendritic spikes, and in proteins that are known to be necessary for synapses to occur following uridine supplementation (6).

dendrite image
Dendrite

Why take Uridine Monophosphate? Here are 5 benefits

#1 – Uridine can stimulate GABA and Dopamine production

As well as uridine’s ability to stimulate synapse, phospholipid production, neuron growth, and acetylcholine production, it can also stimulate Dopamine and GABA production as well as receptor sensitivity to both Dopamine and GABA (7, 8, 9).

By increasing receptor sensitivity it means that Dopamine and GABA neurotransmitters can have a greater effect. Dopamine is associated withfocus and motivation, whereas GABA is associated with relaxation and peace.

#2 – Uridine can help with cognitive development

A further study by Wurtman this time with Lisa Teather looked at young rats who were ready to move from the care of their mothers’. Some of the rats were then kept in ‘Impoverished conditions‘ for 3 months. Impoverished conditions meant that each rat was kept in a bare cage on its own, without toys such as ladders, tunnels, swings, and mazes. The other rats were kept in ‘Enriched conditions‘ which included other rats to socialize with and many toys to play with.

Rats are social animals and thrive when they are able to interact with their environment and learn, so putting them in ‘impoverished conditions’ affects their cognitive development.

Whilst all of the rats were given a full diet, some were also fed Uridine Monophosphate. The researchers found that the rats that were not fed Uridine and raised in ‘impoverished conditions’ had reduced learning and memory.

On the other hand, the rats fed uridine in impoverished conditions actually had memory and learning to a similar level as the rats raised in enriched conditions (10).

#3 – It can help improve sleep quality

Studies in rats have also found that Uridine benefits include helping with sleep, especially slow-wave sleep also known as deep sleep (11, 12, 13).

Slow-wave sleep makes up stage 3 of sleep and it’s considered important for memory consolidation. This means when we turn short-term memories into long-term memories. People that have reduced levels of deep sleep tend to struggle more with memory problems.

#4 – It can help with glycogen or energy production

Perhaps one of the least understood benefits of Uridine is its role in the production of glycogen. Glycogen is stored glucose and it allows us to have an immediate store of energy that can be used whenever it’s needed. Uridine as Uridine Diphosphate Glucose is a direct precursor to glycogen and it can directly activate glycogen synthesis (14).

Not having enough glycogen can be a problem and can lead to us running out of fuel or ‘hitting the wall’ if we’re exercising, or just generally feeling weak and losing focus at any other time during the day.

If it happens overnight, it can lead to us waking up and struggling to go back to sleep. Even for people on fully ketogenic diets, the brain still needs to get around 40% of its energy from glucose / glycogen, so not being able to make enough glycogen can easily cause cognitive problems.

#5 – Uridine can improve your mood with its antidepressant effect

A study by Carlezon et al. at Harvard looked at rats that were given Uridine or the Omega 3 fatty acid DHA or both, and then compared them to control rats on a forced swim test.

The forced swim test is often used in scientific research to judge emotional states and it works by the rodents being put in a plastic cylinder filled with water. The longer the animals swim without giving up is seen to be a measure of how good they are feeling. The test lasts for a maximum of 15 minutes or when the animal gives up and just bobs with its head above water.

Antidepressants have been shown to increase the amount of time that the animals swim for. In this test, both DHA and Uridine were able to increase the rats’ swim time when compared to controls, and both the DHA times and the Uridine times were similar.

It was also found that if the DHA and Uridine were combined, the researchers needed less of each to reach the maximum swim time (15).

What’s the right Uridine dosage for Uridine on it’s Own?

There is currently no official Uridine monophosphate dosage. As demonstrated by clinical studies, Uridine dosage varies. For example:

Healthy adults given 1g of Uridine two times a day for 1 week significantly increased their membrane phospholipids phosphomonoesters (PME) and phosphoethanolamine (PETn) levels. This is important because altered brain phospholipid levels are a characteristic feature in cognitively impaired individuals suffering from conditions like multiple sclerosis, Alzheimer’s, and bipolar disorder (16).

In another study, depressed teenagers with bipolar disorder took 500g of Uridine twice a day. After 6 weeks, the participants showed an improvement in their symptoms (17).

Stacking Uridine Monophosphate, Choline, and DHA

This is not the only study to look at DHA and Uridine. In fact, there have been several studies that have looked at Uridine, DHA, and Choline-rich diets. If you take these 3 molecules you theoretically have everything you need to produce new synapses and neuronal growth.

In fact, Alzheimer’s and other cognitive decline patients exhibit a number of different traits, including a reduced number of brain synapses, dendritic spines, and membrane-rich structures. Specifically, the combination of Uridine, Choline, and DHA has been shown to significantly increase all of these (18, 19, 20). So the possibility remains that supplementing with a combination of these 3 could help prevent dementia.

However, so far the clinical trials in humans have produced somewhat mixed results in that they didn’t provide a significant difference in preventing subjects who had mild cognitive impairment (i.e the first stage of developing dementia) from going on to develop dementia or Alzheimers. Nevertheless, the subjects did show improvement in cognitive tests on attention, memory, and executive function (21, 22).

It may be a case that by the time symptoms of dementia are actually showing there is already too much neuronal damage to be able to reverse it, so the benefit of this nutritional therapy could be in prevention.

Want to try this Uridine, Choline, and DHA stack?

If you would like to try this stack, we recommend the following products:

1) Seneca Nootropic which contains 150mg Uridine Monophosphate, 250mg Citicoline, and 16 other proven nootropics.

2) Ultra Pure Omega 3, which contains 816mg of DHA per 3 capsules serving (along with 1224mg of EPA).

If you want to know more about nootropics, check out this article on “What Are Nootropics?”

References

(1) E.M. Cornford, W.H. Oldendorf, Independent blood-brain barrier transport systems for nucleic acid precursors, Biochim. Biophys. Acta 394 (1975) 211-219.

(2) Mehmet CanSeVa,b, Carol J. Watkins a, Eline M. van der Beek c, Richard J. Wurtman a,d, Oral uridine-5′ -monophosphate (UMP) increases brain CD~-choline levels in gerbils, Brain Research 1058 (2005) 10 I – 108.

(3) Mehmet Cansev, Uridine and cytidine in the brain: Their transport and utilization, Brain Research Reviews, 52 (2006) 389 – 397

(4) K Duchén, L Thorell, Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children, Acta Paediatr 1999 Dec;88(12):1338-43.

(5) Mehmet Cansev, Carol J. Watkins, Eline M. van der Beek c, Richard J. Wurtman, Oral uridine-5V-monophosphate (UMP) increases brain CDP-choline levels in gerbils, Brain Research 1058 (2005) 101 – 108.

(6) Wurtman R.J., Cansev M., Sakamoto T., Ulus I.H. Use of phosphatide precursors to promote synaptogenesis. Annual Review of Nutrition. 2009;29:59-87.

(7) L. Wang, A.M. Pooler, M.A. Albrecht, R.J. Wurtman, Dietary Uridine-5′ -Monophosphate Supplementation Increases Potassium-Evoked Dopamine Release and Promotes Neurite Outgrowth in Aged Rats J. Mol. Neurosci. 27 (2005) 137–145.

(8) R. Guarneri, C. Mocciaro, F. Piccoli, Interaction of Uridine with GABA Binding Sites in Cerebellar Membranes of the Rat, Guarneri, Neurochemical Research. 8 (1983) 1537–1545.

(9) P. Liu, X. Che, L. Yu, X. Yang, N. An, W. Song, C. Wu, J. Yang, Uridine attenuates morphine-induced conditioned place preference and regulates glutamate/GABA levels in mPFC of mice Pharmacolgy, Biochemistry, Behaviour 163 (2017) 74–82

(10) Lisa A. Teather, and Richard J. Wurtman, Chronic Administration of UMP Amelioratesthe Impairment of Hippocampal-Dependent Memory in Impoverished Rats, The Journal of Nutrition Ingestive Behavior and Neurosciences.

(11) Kazuki Honda, Yasuhisa Okano, Yasuo Komoda, Shojiro Inoue, Sleep-promoting effects of intraperitoneally administered uridine in unrestrained rats, Neuroscience Letters, Volume 62, Issue 1, 20 November 1985, Pages 137-141

(12) Toshiyuki Kimura, PhD, Ing Kang Ho, PhD, Ikuo Yamamoto, PhD, Uridine Receptor: Discovery and Its Involvement in Sleep Mechanism, Sleep, Volume 24, Issue 3, May 2001, Pages 251–260,

(13) M Kimura-Takeuchi, S Inoué, Lateral preoptic lesions void slow-wave sleep enhanced by uridine but not by muramyl dipeptide in rats, Neurosci Lett. 1993 Jul 9;157(1):17-20.

(14) Yumei Zhang, Songge Guo, Chunyan Xie, Jun Fang, Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis, BioMed Research International, vol. 2020, Article ID 7091718, 7 pages, 2020.

(15) William A Carlezon Jr, Stephen D Mague, Aimee M Parow, Andrew L Stoll, Bruce M Cohen, Perry F Renshaw, Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats, Biol Psychiatry. 2005 Feb 15;57(4):343-50.

(16) Agarwal, Nivedita et al. “Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T.” Bipolar disorders vol. 12,8 (2010): 825-33. doi:10.1111/j.1399-5618.2010.00884.x

(17) Kondo, Douglas G et al. “Open-label uridine for treatment of depressed adolescents with bipolar disorder.” Journal of child and adolescent psychopharmacology vol. 21,2 (2011): 171-5. doi:10.1089/cap.2010.0054

(18) Sarah Holguin, Joseph Martinez, Camille Chow, Richard Wurtman, The FASEB Journal, Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils, Volume22, Issue11, November 2008

(19) Toshimasa Sakamoto, Mehmet Cansev, Richard J Wurtman, Oral supplementation with docosahexaenoic acid and uridine-5′-monophosphate increases dendritic spine density in adult gerbil hippocampus, Brain Res. 2007 Nov 28;1182:50-9. doi: 10.1016/j.brainres.2007.08.089. Epub 2007 Sep 21.

(20) M. Canseva,b and R. J. Wurtmana, Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils, Neuroscience. 2007 Aug 24; 148(2): 421–431.

(21) Jill Rasmussen, The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer’s disease?, Clin Interv Aging. 2019 Aug 15;14:1481-1492.

(22) Effect of dietary interventions in mild cognitive impairment: a systematic review, Andrea M McGrattan, Claire T McEvoy, Bernadette McGuinness, Michelle C McKinley, Jayne V Woodside, Br J Nutr. 2018 Dec;120(12):1388-1405.