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. Also, find out how our nootropic stack (Seneca Nootropic Complex) can help maximize Uridine’s nootropic powers!
Table of Contents
What is Uridine Monophosphate and what does it do in the brain?
Uridine is a building block of RNA, which allows the body to make proteins. But Uridine is so much more than just RNA. Once absorbed into the body, Uridine Monophosphate can cross the blood-brain barrier (1, 2).
Once in the brain, Uridine can convert into Uridine Tri Phosphate (UTP). Then it further converts into Cytidine Tri Phosphate (CTP) and CDP Choline. When combined with Diacylglycerol, it turns into 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).
Once we have Phosphatidylcholine, we can produce any of the other 3 main phospholipids. These are Sphingomyelin, Phosphatidylserine, and Phosphatidylethanolamine.
These molecules are critical for health. Phospholipids form the basis of our cell membranes. 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, aka the “smart” neurotransmitter, helps with focus, attention, memory, and motivation. Its release from neuromuscular junctions allows our brain 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 what it looks like:
Which is more absorbable? Uridine vs Uridine Monophosphate
Uridine Monophosphate is an important molecule for brain development. It’s found in significant amounts in breast milk and infant formulas (4).
On the other hand, examples of Uridine-rich foods include beer, fish, and broccoli. However, they’re mostly made up of the RNA form, which is not well absorbed in the gut.
Animal studies done by Cansev and Wurtman support Uridine Monophosphate’s superior absorbability (2, 5). Thus, supplementing with Uridine Monophosphate is a good option for those wanting to increase their Uridine levels.
Why take Uridine Monophosphate? Here are 5 benefits
#1 – Uridine can stimulate GABA and Dopamine production
In addition to Uridine’s ability to stimulate synapse, phospholipid production, neuron growth, and acetylcholine production, it can also stimulate Dopamine and GABA production. It also promotes receptor sensitivity to both Dopamine and GABA (6, 7, 8).
Increasing receptor sensitivity means that Dopamine and GABA neurotransmitters can have a greater effect. This means greater focus and motivation because of Dopamine, and more relaxation and peace due to GABA.
#2 – Uridine can help with cognitive development
An animal study selected young rats that were ready to move on from the care of their mothers’. They were kept in either impoverished conditions or enriched conditions for 3 months. Impoverished conditions meant a bare cage, no toys such as ladders, tunnels, swings, and mazes. Meanwhile, enriched conditions meant toys and and other rats to socialize 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.
That said, all of the rats were fed a full diet. Some were also fed Uridine Monophosphate. The researchers found that the ‘impoverished’ rats not given Uridine had reduced learning and memory. On the other hand, the ‘impoverished’ rats fed with Uridine actually had memory and learning on par with the ‘enriched’ rats (9).
#3 – It can help improve sleep quality
Studies in rats have also found that Uridine benefits include helping with sleep, especially slow-wave or deep sleep (10, 11, 12).
Slow-wave sleep makes up stage 3 of sleep. This stage is necessary for memory consolidation, when short-term memories turn into long-term memories. People with 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. It gives us an immediate store of energy that can be used whenever it’s needed.
Uridine as Uridine Diphosphate Glucose is a direct precursor to glycogen. It can directly activate glycogen synthesis (13).
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. We may also generally feel weak and lose focus at any 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
Carlezon and colleagues did an animal study where they gave either Uridine or Omega-3 fatty acid (specifically DHA) or both to rats. Then they compared them to control rats on a forced swim test. This test helps researchers understand the rats’ emotional states, i.e. if they’re feeling good or not.
The rats are placed in a water-filled plastic cylinder. The longer the animals swim, the better they may be feeling. The test lasts for 15 minutes max or when the animal gives up.
The outcome? Both DHA and Uridine helped increase the rats’ swim time. Both DHA times and Uridine times were similar. Moreover, if both DHA and Uridine were combined, the rats needed less of each to reach the maximum swim time (14)!
That said, synthetic antidepressants can also increase the amount of time the animals swim for. This study confirms that Uridine (and DHA) can indeed help improve mood, working similarly to antidepressants.
What’s the right dosage for taking Uridine?
There is currently no official Uridine monophosphate dosage. As demonstrated by clinical studies, Uridine dosage varies.
For example:
Depressed teenagers with bipolar disorder took 500g of Uridine twice a day. 6 weeks later, the subjects showed an improvement in their symptoms (15).
Meanwhile, another study gave 1g of Uridine twice a day for 1 week to healthy adults. This dosage was enough for the subjects’ to significantly increase their membrane phospholipids. This is important because cognitively impaired individuals often have altered brain phospholipid levels (16).
Stacking Uridine, Choline, and DHA together
Several studies 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. This includes a reduced number of brain synapses, dendritic spines, and membrane-rich structures. But the combination of Uridine, Choline, and DHA may help significantly increase all of these (17, 18, 19). So, the possibility remains that supplementing with these 3 compounds may help prevent dementia.
However, so far the clinical trials in humans have produced somewhat mixed results. They didn’t provide a significant difference in preventing subjects who had mild cognitive impairment (first stage of dementia) from going on to develop dementia or Alzheimers. Nevertheless, the subjects made improvements in cognitive tests on attention, memory, and executive function (20, 21).
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-capsule serving (along with 1224mg of EPA).
Check out this article on “What Are Nootropics?” to learn more about how nootropics can help you!
References
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(2) Oral uridine-5′-monophosphate (UMP) increases brain CDP-choline levels in gerbils, Mehmet Cansev, Carol J Watkins, Eline M van der Beek, Richard J Wurtman, Brain Res . 2005 Oct 5;1058(1-2):101-8.
(3) Uridine and cytidine in the brain: their transport and utilization, Mehmet Cansev, Brain Res Rev . 2006 Sep;52(2):389-97.
(4) Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children, K Duchén, L Thorell, Acta Paediatr . 1999 Dec;88(12):1338-43.
(5) Use of phosphatide precursors to promote synaptogenesis, Richard J Wurtman, Mehmet Cansev, Toshimasa Sakamoto, Ismail H Ulus, Annu Rev Nutr . 2009;29:59-87.
(6) Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats, Lei Wang, Amy M Pooler, Meredith A Albrecht, Richard J Wurtman, J Mol Neurosci . 2005;27(1):137-45.
(7) Interaction of uridine with GABA binding sites in cerebellar membranes of the rat, Patrizia Guarneri, Rosa Guarneri, Carmela Mocciaro & Federico Piccoli, Published: December 1983
(8) Uridine attenuates morphine-induced conditioned place preference and regulates glutamate/GABA levels in mPFC of mice, Ping Liu, Xiaohang Che, Lisha Yu, Xiaofeng Yang, Nina An, Wu Song, Chunfu Wu, Jingyu Yang, Pharmacol Biochem Behav . 2017 Dec;163:74-82.
(9) Chronic administration of UMP ameliorates the impairment of hippocampal-dependent memory in impoverished rats, Lisa A Teather, Richard J Wurtman, J Nutr . 2006 Nov;136(11):2834-7.
(10) Sleep-promoting effects of intraperitoneally administered uridine in unrestrained rats, Kazuki Honda, Yasuhisa Okano, Yasuo Komoda, Shojiro Inoue, Neuroscience Letters Volume 62, Issue 1, 20 November 1985, Pages 137-141.
(11) Uridine Receptor: Discovery and Its Involvement in Sleep Mechanism, Toshiyuki Kimura, PhD, Ing Kang Ho, PhD, Ikuo Yamamoto, PhD, Sleep, Volume 24, Issue 3, May 2001, Pages 251–260
(12) Lateral preoptic lesions void slow-wave sleep enhanced by uridine but not by muramyl dipeptide in rats, M Kimura-Takeuchi, S Inoué, Neurosci Lett . 1993 Jul 9;157(1):17-20.
(13) Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis, Yumei Zhang, Songge Guo, Chunyan Xie and Jun Fang, Published: 15 Apr 2020
(14) Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats, William A Carlezon Jr, Stephen D Mague, Aimee M Parow, Andrew L Stoll, Bruce M Cohen, Perry F Renshaw, Biol Psychiatry . 2005 Feb 15;57(4):343-50.
(15) Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder, Douglas G. Kondo, Young-Hoon Sung… J Child Adolesc Psychopharmacol. 2011 Apr; 21(2): 171–175.
(16) Short-term administration of uridine increases brain membrane phospholipids precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T, Nivedita Agarwal, Young-Hoon Sung… Bipolar Disord. Author manuscript; available in PMC 2011 Dec 1.
(17) Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils, Sarah Holguin, Joseph Martinez, Camille Chow, Richard Wurtman, FASEB J . 2008 Nov;22(11):3938-46.
(18) Oral supplementation with docosahexaenoic acid and uridine-5′-monophosphate increases dendritic spine density in adult gerbil hippocampus, Toshimasa Sakamoto, Mehmet Cansev, Richard J. Wurtman, Brain Research Volume 1182, 28 November 2007, Pages 50-59
(19) 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, M Cansev, R J Wurtman, Neuroscience . 2007 Aug 24;148(2):421-31.
(20) The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer’s disease? Rasmussen J, Published 15 August 2019 Volume 2019:14 Pages 1481—1492
(21) 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.
