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All You Need to Know About Uridine and its Effects on The Brain

Uridine is a component of RNA that has positive health effects on humans. It can help improve brain function and aid in treating mental disorders, reduce pain, and protect the heart. Read more below to find out all about the benefits of uridine.

Introduction

Uridine is one of 5 nucleosides that make up a nucleic acid. It is an important component of RNA and plays a big role in central nervous system function (R).

In adults, uridine is synthesized in the liver as uridine monophosphate (UMP) and secreted as UMP in the blood. Uridine can also be found as uridine triphosphate or uridine-5′-monophosphate (R).

It is found in many types of plants and is also present in breast milk (R).

Uridine is also involved in the glycolysis pathway (R).

My Personal Experience With Uridine

I’ve been taking uridine on and off for years, and the effects are subtle even when I take experimental dosages (1.5g).

I take this merely because I think it’s helping my brain even if I don’t notice it acutely.  I’m not worried about potential side effects as they seem minor.

I take 250mg of uridine a day (with DHA and choline) as a nootropic to increase cognitive performance over the long term.

What I Recommend

You should use these if you don’t want any excipients:

The Jarrow uridine linked is also good, but has some excipients.

Uridine Snapshot

Uridine Snapshot

  • Longevity7.0/10
  • Inflammation7.5/10
  • Mood8.0/10
  • Cognition9.0/10
  • Energy7.5/10

Pros

  • Cognitive enhancer
  • Helps protect the brain and improve memory
  • Reduces pain and inflammation
  • Protects the heart
  • May prevent osteoporosis
  • May help treat depression, cystic fibrosis, bipolar disorder, etc.

Cons

  • Can spread cancer
  • Can cause heart disease
  • Side effects include fever and diarrhea

Health Benefits of Uridine

1) Uridine Grows the Brain

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A combination of uridine, DHA, and choline can help increase the number of synapses that are formed in the brain (R).  These three nutrients have a synergistic effect.

Uridine administration was shown to improve sleep, prevent epilepsy, and promote plasticity (changing of the brain’s structure and function) (R).

Uridine administration helped increase slow wave sleep in sleep-deprived rats (R).

Depending on the dosage, uridine also helped stop epileptic episodes in rats. Three injections a day prevented seizures while only one injection did not do anything (R).

Brain plasticity improved after four continuous days of uridine dosage. Neurite filaments and neurites increased in brain cells (R).

In gerbils, uridine monophosphate with choline and DHA led to enhanced cognitive function. Synaptic proteins and neurotransmitter increased after supplementation, and the gerbils’ performances on brain exercises greatly improved (R).

Uridine activates the P2Y2 receptor, which helps with neurite outgrowth (R).  This receptor potentiates the effects of neurotrophins (such as NGF) in neuronal development and regeneration.

P2Y2 receptors are required for enhanced neuronal differentiation and increase growth-associated protein-43 (GAP-43), a marker for axonal growth (R).

The P2Y2 receptor is believed to play an important role in neuroprotection under inflammatory conditions.  The receptors are increased under inflammatory conditions (IL-1b) for this reason (R, R2).

2) Uridine Improves Memory

Long-term exposure to uridine also increases memory in both humans and rats.

When supplemented with choline, verbal and logical memory in humans improved (R).

Uridine can help delay symptoms of Alzheimer’s by stimulating synapse formation (R).

In rats, learning and memory skills improved. Memory dysfunction related to hippocampus damage was also alleviated (R).

Rats given uridine-5′-monophosphate also had increased acetylcholine (R) and dopamine (R).

3) Uridine Reduces Pain and Inflammation

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Patients suffering from carpal tunnel syndrome took a daily capsule of uridine monophosphate and folic acid + vitamin B12. Their pain score was lowered as well as the intensity of pain and symptoms (R).

Oral administration of uridine triphosphate combined with vitamin B12 and cytidine resulted in less back, neck, and hip pain in humans (R).

Uridine supplementation was also shown to relieve inflammation and lung fibrosis symptoms in mice by reducing pro-inflammatory cytokines (R).

When testing was done on human lung cells, uridine also showed anti-inflammatory effects (R).

4) Uridine Helps Protect the Heart

When there is not enough blood supply to the heart, it prevents the heart from receiving enough oxygen. In rats, uridine and uridine-5′-monophosphate can both normalize the heart and stabilize the heart’s rhythm by increasing blood flow (R).

Uridine triphosphate can lessen heart contractions during heart attacks by activating P2Y2 receptors (R).

Uridine/Adenosine causes vasodilation through eNOS in blood vessel cell lines in response to blood flow (via P2Y2 receptor). Mice with P2Y2 deficiency lacked flow-induced vasodilation and developed hypertension that was accompanied by reduced eNOS activation (R).

5) Uridine Restores Liver Growth

In rats, after liver transplants, uridine treatment can help restore liver regeneration. Liver and liver cell growth were both completely restored (R).

6) Uridine Can Help Treat Depression, Bipolar Disorder and Helps Mitochondrial Function

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Bipolar disorder may be influenced by mitochondrial dysfunction. Uridine has been proven effective in preventing problems with the mitochondria in human cells (R).  

In adolescent humans, uridine treatment was helpful in preventing depressive symptoms. The patients did not undergo any negative effects and did not go through any adverse events (R).

In rats, uridine alleviates symptoms of depression (R).

7) Uridine Supplementation Helps With HIV-Related Problems

Lipoatrophy is abnormal loss of fat in parts of the body, and it can occur in HIV-positive patients. HIV-positive patients have a lower uridine level in their blood than healthy patients (R).

In HIV-infected humans, 24 weeks of uridine supplementation resulted in an increase in limb fat. However, this effect was not shown after 48 weeks, but it could be due to the weak dose of uridine and does not mean that there is not a beneficial effect (R).

Long-term antiretroviral therapy used to treat HIV might result in problems with the mitochondria in human patients’ cells and cause toxicity (R).

Uridine supplementation in humans can reverse the toxic effects and prevent mitochondrial depletion (R).

8) Uridine May Aid in Cystic Fibrosis Treatment

Cystic fibrosis is a genetic disorder that damages the lungs and digestive system. Sodium absorption increases secretions in the lungs, which can cause breathing problems (R).

Uridine can increase Cl- secretion, which will cause less thick secretions in the lungs, which makes mucus easier to get rid of. Uridine triphosphate, with the addition of sodium channel blockers, can relieve cystic fibrosis symptoms in mice (R).

Uridine 5′-triphosphate and amiloride can enhance airway and clear mucus in adult human cystic fibrosis patients. They can clear the airways of patients to almost normal levels (R).

9) Uridine Helps Anemia

In a double-blind trial, the combination of vitamin B12, uridine and cytidine was found to be safe and effective in the treatment of the signs and symptoms of anemia in the population studied. The pain reduction observed in both groups may be attributed to activity of the uridine and cytidine (R).

Other

Uridine can blunt the increase in striatal dopamine from cocaine (R).

Is Uridine Right For You? The Genetics of Uridine

UTP stimulates the P2Y2 receptor, which is the pathway by which it stimulates neurons.  I would presume that if these SNPs aren’t working well, then you would probably be a better responder to Uridine.

A point I bring up often is the cancer/autoimmune tradeoff.  P2RY2 activation is good for autoimmune conditions, but not so great for most cancer:

P2RY2 enhances proliferation, adhesion, migration of cancer and increases the immunosuppressive ability of Tregs.

Activation of T Regulatory Cells (Tregs) is on the whole bad for cancer, but good for autoimmune conditions.

If you have 23andme, you can check these SNPs out:

  1. RS10898909 (P2RY2)
  2. RS1783596 (P2RY2)
  3. RS4944831 (P2RY2)

Negative Effects of Uridine

High doses of uridine can induce fevers and cause diarrhea in humans (R).

I am not worried about these side effects for healthy people.  You can find potential side effects with anything if you include test tubes and theoretical models.

However, it’s important to bring them up in case you have a specific condition that is brought down – as a precaution.  So if you already have cancer, thickened heart valves, osteoporosis, or diabetes, I would not take uridine.

It’s also important to note that ATP activates the same receptors as uridine and it’s ubiquitous in the body.

1) Uridine and Cancer

Pharmacological use of uridine may be carcinogenic (R).

Uridine triphosphate can activate the P2Y2 receptor. The P2Y2 receptor increased the spread of human pancreatic cancer cells in bovine cell samples (in vitro) (R).

P2Y2R and uridine triphosphate may play an important role in cancer metastasis when tested in breast cancer lines (R).

Activation of P2Y2 receptor could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1) (R).

It could also increase and help spread liver cancer in a cell model (R).

Another possible way that uridine can cause cancer is by incorporating itself (Uracil) into DNA instead of Thymine (R, R2).  If this were a mechanism, then adequate folate should help.

In contrast, dietary uridine supplementation reduced intestinal tumor number and tumor burden by 40% relative to the control diet in mice (R).

2) Uridine Triphosphate and Heart Disease

In rats, uridine triphosphate induced cardiac fibroblast responses by activating P2Y2 receptors. Fibrosis (thickening of heart valves) might lead to heart failure (R).

3) Uridine and Insulin Resistance

In rats, large amounts of uridine infused into the blood cause insulin resistance (R).

In humans, patients with diabetes had higher concentrations of uridine than healthy patients (R).

However, when human cells were tested, uridine diphosphate and uridine triphosphate were shown to increase insulin secretion (R).

4) Uridine Triphosphate Can Inhibit Bone Formation

UTP (via the P2Y2 receptor on osteoblasts) at low concentrations strongly inhibit bone mineralization and formation (via P2Y2) (RRR).

Uridine triphosphate prevented osteogenesis (which causes bone growth) and increased adipogenesis (R).

Sources of Uridine

Buy Uridine

These are good options for uridine:

Technical

  • P2RY2 can induce IL-6 and IL-8 secretion.
  • UTP promotes alkaline phosphatase (ALP) activity and bone mineralization, and increases the levels of ALP, bone morphogenetic protein (BMP)-2, BMP-4, BMP-5 and bone sialoprotein (BSP) through the P2Y2 receptor in rat primary ostoblasts (R).
  • P2RY2 enhances proliferation, adhesion, migration of cancer and increases immunosuppressive ability of Tregs (bad for cancer, good for autoimmune conditions).
  • Uridine significantly elevated Uridine Triphosphate (UTP) and CDP-choline levels (R).
  • CDP-Choline is synthesized from uridine (R).
  • Uridine generates both Cytidine Triphosphate (CTP), which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis (R).
  • Uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils (R).
  • Potassium (K+)-evoked striatal dopamine release was significantly greater among UMP-treated rats, i.e., 341+/-21% of basal levels vs. 283+/-9% of basal levels in control rats (p<0.05) (R).
  • UTP stimulates the P2Y2 receptor and, following degradation to UDP, also acts on the P2Y6 receptor (R).
  • Uridine triphosphate-induced proliferation was mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increased phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K (R).

Comments

  1. Garry

    What is the difference between pharmacological use of uridine which increases risk of cancer versus dietary supplementation which reduces risk of cancer. Uridine monophosphate seems to have numerous benefits which I would like to explore, but I do not want to increase the risk of cancer. How can Uridine monophospate be taken without increasing risk of cancer? ie. supplementally. Is this by keeping dosage below a certain level or by combining with other nutrients? Thank you.

  2. Thepractice

    These “21 Benefits of Supplement X” and “All you need to know about supplement Y” articles are dissapointing me. Seem to be for SEO purposes.

      • John jihn

        I agree to some extend, but they are still helpful… They give a good overall overview but they lack in the aspect of getting a deeper understanding of the substance and how it works.. I feel like they should be some kind of sidebar material.. These articles are also less likely to be affected by tunnel vision..

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