Uridine monophosphate is a pyrimidine nucleoside that is found in cells of almost all living organisms including bacteria. (1) Uricyl, its active compound, is one of the three distinct chemical groups of repeating units that make ribonucleic acid (RNA) besides the 5-carbon sugar (ribose and deoxyribose), and a nitrogen base (adenosine, guanine, thymidine, and cytidine). RNA a close cousin of DNA, does more than driving protein synthesis as widely known- it also plays a role in catabolism and numerous other cellular responses. (2 ) Uridine monophosphate is also a primary building block for the synthesis of neurons and synapses.
The food sources of uridine include beer, breastmilk, offal (liver and pancreas), barley, baker’s yeast, sugar cane extract, and vegetables. (3 ) Although regularly eating these foods ensures that the body’s levels of uridine remain constant, it does not reliably elevate uridine monophosphate in the brain. The monophosphate portion of uridine is the transporter that assists uridine to move through the gastrointestinal tract unharmed and to cross the blood-brain barrier (BBB). Therefore, although uridine is present in many foods, most of the nootropic benefits are realized through dietary supplementation. (4)
When taken as a nootropic supplement, uridine monophosphate is almost exclusively catabolized in the gastrointestinal tract and the liver. When absorbed into the bloodstream, it readily crosses the BBB where it exerts its nootropic benefits. In the brain, uridine monophosphate works in several ways. First, as a significant building block in the brain, it enhances the growth of neurites, which are growth of projections from neurons that facilitate connections with other neurons. (5) When the number of synapses increases, various aspects of cognition improve.
Second, it increases the levels of neurotransmitters, though indirectly. One of those indirect ways is by increasing the level of phosphatidylcholine in the brain, which in turn boosts the release of acetylcholine and dopamine. (6) Along with its functions in the central nervous system, uridine monophosphate also plays a role in carbohydrate metabolism and cell rejuvenation by supporting the function of mitochondria and hepatic cells.
The brain is arguably the most critical organ in the human body as it controls and coordinates everything from thoughts, actions, memory, feelings to movement. Uridine monophosphate is beneficial for brain plasticity as it helps increase synapse formation (synaptogenesis). It initiates P2Y2 receptors, which aid in neuronal development, regeneration, and synaptic protein synthesis. (7) P2Y2 receptors stimulate outgrowth of neurites, giving them a unique role in integrating neuronal and glial cellular circuits.
Just like most other purines and pyridines, uridine monophosphate is also known to increase neuronal growth by activating nerve growth factor (NGF) through TrkA receptors. NGF just like its name suggests, is a neurotrophic factor that is primarily involved in regulation of growth, maintenance, multiplication, and survival of neurons. (8, 9) Through these two actions, the brain can grow and repair itself more effectively.
Memory is mainly dependent on the plasticity of the brain, which is associated with the ability to turn experiences into memories. Exposure to uridine monophosphate increases memory, particularly verbal and logical memory. It is involved in long-term potentiation in the brain, a process in which memories are created and stored. That is why low levels of uridine in the brain result in memory formation impairment and a decline in synaptic plasticity. (10)
As mentioned above, uridine monophosphate helps in synaptogenesis and boosts the levels of phosphatidylcholine (PC). A phosphatidylcholine-enriched environment enhances hippocampal and striatal dependent memory tasks. Pre- and post-synaptic proteins, dendritic spines and synapses are also increased to strengthen hippocampal types of memory. (11) These memory enhancement benefits are most likely seen after long-term exposure (4 weeks). (12)
Besides its well-characterized role in the neurons, uridine monophosphate also attenuates inflammation. (13) This is a protective function that is not only beneficial to the brain but also other body tissues. Interestingly, uridine is a potent inhibitor of leukocyte adhesion, the key player in inflammatory responses. Aside from that, uridine also reduces the intensity of pain and other symptoms of inflammation effects.
Inflammation is usually a direct reaction to damage of tissue at a cellular level. For an athlete, an inflammatory cascade is activated after each tough workout, to repair whatever may have been done by micro tears. On the flip side, this inflammation is beneficial in the short term. When inflammation is high and persistent in the body, it results in not only muscle damage but also various chronic conditions. (14) Too much inflammation thus reverses strength and muscle gains.
As an anti-inflammatory agent, uridine monophosphate thus promotes positive muscle strength by preventing muscular tissue damage.
As a precursor of cytidine diphosphate (CDP)-choline, uridine monophosphate contributes to the synthesis of phospholipids, which are essential constituents of mitochondrial membranes. (15) Mitochondria are the powerhouses that most of the energy-producing processes take place, and therefore, are critical body-fuelling cellular parts. With optimal healthy mitochondria cells, the body is ordinarily ready for robust fatigue responses and activity endurance.
Moreover, uridine monophosphate translates to a better physical performance by directly influencing the energy-production processes. Energy production revolves around the rebuilding of ATP and other nucleoside triphosphates such as GTP, CTP, TTP, and UTP. ATP is produced in three main cellular processes which include glycolysis, beta-oxidation, and the citric acid cycle. Uridine has a vital role in the galactose glycolysis pathway since galactose-1-phosphate obtains a uridyl group from uridine diphosphate glucose. (16) The sum of these reactions is the effective conversion of galactose into glucose.
Another astounding cognitive benefit of uridine monophosphate is that it impacts on mood by stimulating the release of feel-good neurotransmitters such as dopamine. (17) Dopamine, also known as “the motivation neurotransmitter,” is mostly responsible for feelings of pleasure and reward. Having steady levels of dopamine in specific areas of the brain is thus vital for motivation, attention, and learning.
Uridine is also known to combat stress by reducing the harmful effects of cortisol. (18) The brain as the central organ of stress response, determines what is stressful as well as the behavioral and physiological responses to the stressors. One of those responses is the release of cortisol. Cortisol is only helpful when responding to acute stressors. Chronically elevated cortisol levels only worsen the stress and increase the risk for depression.
Adding uridine monophosphate to the stack is thus a natural way to boost a good mood throughout the day, increase alertness and avoid depression.
Uridine monophosphate not only contributes to synaptogenesis but is also a secret weapon for the neurons. The neuroprotective activities of uridine monophosphate are several. First, as an intermediate of cell membrane phospholipids, it protects the neuron membranes and Schwann cells of the myelin sheath. (19) Demyelination or damage of the Schwann cells slows down neuronal communication, lowering cognitive performance. By preventing damage to these cells, uridine protects that neuronal covering and even helps in treating myelin sheath lesions.
Uridine further prevents fatty acid accumulation of free fatty acids around neurons, alleviating ischemia. If these acids are allowed to accumulate in the brain, they increase inflammatory reactions, free radicals and cause breakdown of neuronal membranes. Moreover, through promoting the release of neurotransmitters, uridine improves neuron coordination, put the brain in a constant active state, preventing decline as a result of disuse. (20) Uridine also inhibits oxidative stress by scavenging free radicals and combating inflammatory responses. (21)
Uridine Monophosphate is taken orally or sublingually. When taken sublingually, it is 7 to 10 times more potent than when taken orally. (22) However, when taken sublingually, users have reported a slight burning sensation. The supplements are mostly available in capsule and powder forms. It is recommended that uridine monophosphate should be taken in doses between 50mg and 1g per day. To start with, most users adopt 150 to 250mg dosage twice daily, then scale upwards to find the optimal dose. With very low doses, it will take a long time to realize the benefits.
One can take uridine monophosphate alone. However, it is generally consumed as a stack. It is suggested that when uridine monophosphate is taken with choline or omega-3, its effects increase manifold after reaching the central nervous system. (23) Given together, they all increase phosphatidylcholine in the brain and accelerate the formation of synaptic membranes, improving cognitive functions. (24)
Uridine monophosphate is well-tolerated in the body and is safe as it is naturally produced in the body. Therefore, users only experience minor side effects such as a decrease in emotions, headaches, nervousness and some gastrointestinal distress. Most of these side effects are reported when using very high doses. Uridine monophosphate is also known to have an effect of depleting the levels of B vitamins and especially B12. (25) To combat this issue, it is prudent to also include B-complex vitamins in your daily supplements.
Here is a summary of the basics of this brain booster.
Also known as 5’-uridylic acid. It is a uracil nucleotide that has one phosphate group esterified at the 5’ sugar moiety position. It thus consists of a phosphate group, pentose sugar ribose, and nucleobase uracil.It is an indispensable part of the nucleus as it is one of the nucleosides that constitute nucleic acid in RNA.Uridine occurs naturally in living cells, after being produced by the liver. Dietary sources include beer (highest content), baker’s yeast, liver, pancreas, cruciferous vegetables, and breastmilk. The problem with uridine from food sources is that most of it never makes it from the digestive system to the brain, thus the need for supplementation.In supplementation, the phosphate group increases the bioavailability and helps it to cross the blood-brain barrier.It works by being a precursor of brain synapses and nerve cell membrane phospholipids, enhancing cholinergic functions of the brain and lastly by supporting the liver and mitochondria.Uridine monophosphate encourages brain growth through activation of P2Y2 and TrkA receptors. P2Y2 receptors stimulate the growth of neurites while TrkA receptors boost the levels of nerve growth factor.Improves memory by promoting neuroplasticity of the brain and enhancing hippocampal and striatal dependent memory tasks. The memory benefits are seen mostly after four weeks of supplementation.Promotes mitochondrial health by increasing the levels of phospholipids, which are components of healthy mitochondrial membranes.Uridine Monophosphate also supports mitochondria by taking part in the conversion of galactose into glucose.Protects the muscles and brain from inflammation and reduces pain by inhibiting leucocyte adhesion and accumulation of pro-inflammatory cytokines.Improves mood and alertness by elevating the levels of dopamine and lowering those of cortisol.Uridine monophosphate can be taken in doses between 50mg and 1g daily. For starters, a dose not exceeding 250mg twice is recommended. The user can then adjust the dose upwards as time goes.It is well-tolerated and has minimal side effects, which are mostly reported with higher doses.