TLDR
Helps produce CDP-Choline, Phosphatidylcholine, Acetylcholine
Shown to improve Memory, Learning, Focus
May help with various diseases
Typical dose is 250-500 mg twice a day
Table of Contents
What Is It
Uridine, pyrimidine nucleoside, is one of 4 repeating units that make up RNA (Ribonucleic Acid). RNA and DNA (deoxyribonucleic acid).
Importantly for us, Uridine is a substrate in Phosphatidylcholine (PC) synthesis via Kennedy cycle (aka CDP-Choline pathway, shown below). Uridine Monophosphate (UMP) is a form of Uridine with a phosphate group attached which has been shown to increase its absorption and utilisation in the brain. Once in the body, UMP can cross the blood-brain barrier to enter the brain [1,2].
There, it is important for the synthesis of Cytidine Triphosphate (CTP) which is the rate limiting step in the production of CDP-Choline [3], which then leads to the synthesis of PC (along with Diacylglycerol, a substrate made from DHA/EPA from fish oil which is important when we consider other compound to stack).
From PC we can also then produce acetylcholine, the primary neurotransmitter used by your nerves important for focus, memory and attention as well as at the neuromuscular junction for your muscles to function.
Once we have Phosphatidylcholine, we can produce any of the other 3 main phospholipids. These are Sphingomyelin, Phosphatidylserine, and Phosphatidylethanolamine.
These are important molecules needed for our cell membranes including those of our neurons and the myelin sheaths surrounding our nerves, among other uses. PC and Sphingomyelin form the outside layer of our cell members and PS and Phosphatidylethanolamine form the inside layer [4].
The uridine found in food is mostly in the RNA form and is poorly absorbed when compared to UMP [2,5].
Uridine has also been shown to act as a purinergic neurotransmitter to the P2 receptors and assist with neurite growth via nerve growth factor (NGF) and TrkA. This is an important part of maintaining nerve health and for learning and memory. [6,7]
Research and Benefits
Improve Memory and Learning
As mentioned above, uridine creates the right environment for increased neuronal plasticity and synapse formation, which may help the brain adapt, learn, remember, and regrow.
A human study of 26 elderly people concluded that Uridine along with other nutrients (as Cognitex®) caused a "significant improvement in memory abilities (recall, recognition, and spatial short term)". [8]
A human study of supplementing Uridine with Choline saw improvements in verbal and logical memory. [9]
An animal study found that Uridine improved memory and learning. [10]
A gerbilstudy combining Uridine, Choline and DHA (found in omega 3) resulted in improved memory and learning, increased neurite outgrowth and increased Acetylcholine release. [11]
Uridine was seen to "amplify" the functionality of Acetylcholine in rats, the learning neurotransmitter that is used by neurons to communicate with each other. [12]
Stimulate Dopamine Release
A study in rats using a form of UMP (UMP-2Na+) showed an increase in dopamine release of 11.6-20.5% along with increased neurite outgrowth. [13]
Neurodegenerative Disease
Administration of UMP and DHA in a rodent model of parkinsons was shown to improve dopaminergic neurotransmission (more than DHA alone). [14]
May assist with Alzheimer’s disease as this disease is associated with reduced synaptic function. In 1 study a multi-nutrient consisting of Uridine with DHA/EPA and other micronutrients reduced Alzheimer’s like pathology in a rodent model. [15,16]
Narrative review by Baumel et al. suggests that a combination of UMP, Choline, DHA may work synergistically to repair pathological shortage of these substrates in the Alzheimer’s brain/ [17]
Bipolar Disorder
In a study of seven adolescents with bipolar disorder, uridine prevented depressive symptoms. It may work by improving mitochondrial function, which is thought to be compromised in bipolar brains [18].
A study of 17 healthy people revealed that uridine improves the phospholipid structure of the nerve cell membrane. Membrane phospholipids may be altered in people with bipolar disorder [19].
Cardioprotective
In a rat study, uridine normalized the heart’s rhythm by reactivating energy metabolism. It was most effective as uridine-5′-monophosphate (UMP) [20].
By activating P2Y2 receptors, uridine might also improve heart health. In a combined animal and cell study, P2Y2 receptor activation increased blood flow and improved blood pressure [21].
Improve Sleep
In rats, uridine promotes slow-wave (deep) sleep, which is the most restorative phase of sleep [22].
Dosing
There is no clinically advised dosing at this time for UMP. General recommendations at the moment are 250-500 mg twice daily (500 – 1000 mg per day).
It will take time for the effects to be noticed but should be seen by around 1-2 weeks.
It is important for you to test out different doses and see what works best for you.
Stacks
As we’ve seen, there are a few synergistic nutrients that work well with UMP.
Alpha GPC: 300 mg per day
Fish Oil (DHA/EPA): 1-2 g per day
Lions Mane: some neurohackers have been using Lion’s Mane or other medicinal mushrooms as a stack with the above, typical dose for Lion’s Mane is
Where to Buy
UMP is pretty common, always try to find sources with as little additives as possible.
Side Effects / Warnings
As uridine is a natural product found in food, it is typically safe and well tolerated. However there is little research on the safety and side effects of higher dosing.
Some people have reported anhedonia at high doses
Activation of the P2Y2 receptor by UTP may induce pancreatic cancel cells [23]
Always consult your doctor before adding any supplements into your routine.
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