Uridine: A Key for Synaptogenesis [Mirror]


Research Roundup:

Uridine Function in the Central Nervous System

Arpád Dobolyi, Gábor Juhász, Zsolt Kovács, and Julianna Kardos 

“Emerging evidence suggests that uridine is a neuroactive molecule, which is involved in the regulation of certain neural functions apart from its role in pyrimidine metabolism. Uridine has sleep-promoting and anti-epileptic effects, might affect mood, improves memory function and influences neuronal
plasticity. Evidence for the existence of uridine sensitive neurons is also convincing. These actions are likely to be exerted via its actions on membrane formation, by the known uridine nucleotide receptors, or even on its own putative receptor predicted in plasmamembranes or intracellular binding sites in the central nervous system. Since uridine, as a dietary component, is not toxic and has access to the brain from the plasma through transporters, it is an appealing lead molecule for the development of drugs with central site of action. Based on its actions, the therapeutic application of uridine and its derivatives are being explored.” (CITE)

A Nutrient Combination that Can Affect Synapse Formation

Richard J. Wurtman

“Brain neurons form synapses throughout the life span. This process is initiated by neuronal depolarization, however the numbers of synapses thus formed depend on brain levels of three key nutrients—uridine, the omega-3 fatty acid DHA, and choline. Given together, these nutrients accelerate formation of synaptic membrane, the major component of synapses. In infants, when synaptogenesis is maximal, relatively large amounts of all three nutrients are provided in bioavailable forms (e.g., uridine in the UMP of mothers’ milk and infant formulas). However, in adults the uridine in foods, mostly present at RNA, is not bioavailable, and no food has ever been compelling demonstrated to elevate plasma uridine levels. Moreover, the quantities of DHA and choline in regular foods can be insufficient for raising their blood levels enough to promote optimal synaptogenesis. In Alzheimer’s disease (AD) the need for extra quantities of the three nutrients is enhanced, both because their basal plasma levels may be subnormal (reflecting impaired hepatic synthesis), and because especially high brain levels are needed for correcting the disease-related deficiencies in synaptic membrane and synapses.” (CITE)

A Critical Evaluation of the Available Information on the Toxicity/Safety of Orally Administered Uridine

J. F. Dorzelleca

“[u]ridine is a rather safe drug in humans at least at doses up to 10 grams.” (CITE)

What is Uridine Monophosphate (UMP)?

As you may have read on this or other pages, UMP is important for the growth of new brain cells, but to understand what UMP is, we first have to take a quick look at our own DNA. Our DNA looks like a twisted ladder, or what scientists call a “double helix”.
RNA is basically half of that ladder, and as you will soon see, UMP is a key part of RNA. mRNA (messenger-RNA) actually glides into the nuclear pores to encode and communicate with the DNA in the nucleus at center of a cell. These processes are what create, and maintain our cells.
In this article, I am going to explain how UMP benefits your brain, and how it helps create new neurons with the help of choline and DHA (docosahexaenoic acid). There are so many studies using all three ingredients together for brain health.

A Little Review…

Inside your cells, inside the nucleus in the center of the cell is your DNA. Its language consists of only four letters: A C T G. This stands for Adenine, Cytosine, Thymine, and Guanine.
This seems deceptively simple, and I think too many people assume that we know all there is to know about DNA now. Nothing could be further from the truth.

Back to Uridine Monophosphate…

As you may have noticed as we look at a zoomed in version of DNA and RNA, there is one base pair that is different than the other. Instead of thymine, RNA has a unique nucleobase called uracil. Take note of the “helix of sugar-phosphates” portion of the diagram above.

That phosphate spine and the ribose sugar are what gives DNA and RNA their characteristic double helix shape. UMP (uridine monophosphate) is the uracil plus the ribose sugar and one phosphate ion.

Uridine and the Brain

Uridine that is missing the phosphate group would not enter our body through our digestive tract. The phosphate group gets the uridine into our bodies and brains through the digestive tract. Higher levels of uridine in the brain lead to a greater density of synapses in the brain. (CITE
This was one of those studies that they did with UMP, choline (CDP-choline aka Citicoline), and DHA used together. This combination was shown to improve problem-solving skills and memory, especially over time.

More Studies About Uridine

Another thing about uridine is that raises levels of CDP-choline in the brain, and taking CDP-choline will increase brain levels of uridine.
A study from the NIH stated:

“In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents.”(CITE)

Uridine may function like a novel neurotransmitter in the brain with calming and neuroprotective benefits. Uridine are also connected to the regulation of dopamine and acetylcholine which aid with focus and motivation. (CITE) (CITE)
CDP-choline can also increase the density of acetylcholine receptors and dopamine receptors in the brain.Oddly enough, we actually become more sensitive to these neurotransmitters over time as we use CDP-choline to raise our neurotransmitter receptor density. (CITE)
Read our Full Article on Choline here.

Other Benefits of Uridine Monophosphate

3D Model of Uridine Monophosphate

Other benefits of UMP include being protective of cardiovascular health (CITE), reducing pain and inflammation (CITE), it can help restore the liver (CITE), it aids mitochondrial function, and it can also help with bipolar disorder and depression (CITE).
The study done about depression and bipolar was done on teenagers who took uridine monophosphate for 6 weeks taking 500mg twice daily and none of them reported any negative side effects. Many of them also reported benefits in regards to their depression and bipolar disorder.
There is also a lot of research out there uridine monophosphate especially with DHA and choline in addition to the supplemental uridine monophosphate.
Read our Full Article on DHA here.

Potential Side Effects

The side effects are very mild if felt at all. A maintenance dose of UMP is only take about 150 mg – 300 mg per day, but throughout a brain disease process it can help immensely to supplement much higher doses of UMP. The only side effects that have been shown at high doses are fever and upset stomach (Doses as high as 1-2 g), however, the FDA has determined up to 10 grams per day will not cause harm to humans. (CITETaking UMP with food can reduce incidence of nausea or upset stomach.

Supplement Combination for Brain Optimization

Combining uridine monophosphate, DHA, and CDP-choline is already a winning combination, but adding some CoQ10 to boost ATP can take your stack to the next level. Creatine has a similar effect of boosting ATP production.
Read our Full Article on ATP here.
Another great addition to this is to add some kind of antioxidant. I like to use various kinds of antioxidants like Nano-liposomal glutathione, curcumin extract from turmeric, EGCG extract from matcha green tea, proanthocyanidins from blueberries, resveratrol extract from red grapes (or Japanese knotweed) or any other kind of antioxidant like naturally pigmented foods.
This allows you to reduce levels of inflammation, and to increase energy output from your cells. This is the basis of most of the damage caused by a brain injury and even age-related cognitive decline and aging in general. Add uridine to your day for more memory, focus, and synaptogenesis.