Uridine is a component of RNA that may improve brain function, relieve depression and nerve pain, and protect the heart. Research reveals it might strengthen and restructure your brain synapses, enhancing learning and memory. Read on to discover its benefits, side effects, and science-based stacks.

What is Uridine?

You’ve heard of DNA, the tiny double helix that encodes all of your genes, but have you heard of its sibling molecule, RNA? Where DNA stores your genetic information, RNA (which is short for ribonucleic acid) translates it into proteins.

As another difference, RNA uses a ribonucleotide called uridine (the nucleotide uracil bound to a ribose sugar) to translate the DNA code [1, 2].

Besides its role in RNA, uridine helps your body break down sugar for energy. It plays a big role in your brain and cognitive function [3, 4].

In adults, the liver creates uridine in the form of uridine monophosphate (UMP) and secretes it into the blood. Uridine can also exist as uridine triphosphate or uridine-5′-monophosphate [5, 6].

Snapshot

PROs

  • Enhances cognitive function
  • Reduces nerve pain
  • Protects the mitochondria
  • Improves the symptoms of lung diseases
  • May help with depression and bipolar disorder
  • May improve sleep quality

CONs

  • Not recommended for those with cancer, fibrosis, diabetes or osteoporosis

Benefits of Uridine

1) Enhances Learning & Memory

Your brain uses uridine to create CDP-choline, a well-known memory enhancer, and other brain phospholipids. In a study of 17 healthy volunteers who underwent brain imaging, uridine supplements increased their brain levels of phosphoethanolamine (PEtn), an important phospholipid building block [7].

Uridine creates the right environment for increased neuronal plasticity and synapse formation, which helps the brain adapt, learn, remember, and regrow [8, 9].

In cell and animal studies, uridine increased neurite outgrowth, a process that helps brain cells grow and regenerate [8, 9].

In the same studies, uridine also increased synaptic proteins, small molecules found in the cleft or synapse that brain cells use to communicate. When these proteins drop, synapses get destroyed. Only later do brain cells die and memory problems arise, as in Alzheimer’s disease [8, 9, 10].

Lastly, uridine enhanced dendritic spines, the “back” of neurons thought to store memory [8, 9, 11].

Two gerbil studies came to a similar conclusion. In one, uridine monophosphate in combination with choline and DHA enhanced cognitive function. In the other, uridine and DHA increased phospholipids and synaptic protein levels in the animals’ brains [12, 13].

Uridine activates the P2Y2 receptor, which, alongside nerve growth factor (NGF), promotes the birth of new neurons and regeneration of injured ones [14, 15].

An active P2Y2 receptor likely protects neurons from injury in the first place. It becomes more active under inflammatory conditions, such as when interleukin-1b (IL-1b) is high, to protect the brain [16, 14].

Uridine promotes the birth of new neurons and the generation of new synapses, especially in combination with brain nutrients like choline and DHA. Human studies have yet to confirm these findings, but animal studies are very promising.

2) May Protect the Heart

When your heart doesn’t get enough oxygen, your heart may suffer damage. The arteries supplying the heart are usually either partially or completely blocked, most commonly due to fatty plaques [17].

In a rat study, uridine normalized the heart’s rhythm by reactivating energy metabolism. It was most effective as uridine-5′-monophosphate (UMP) [18].

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 [19].

Uridine may maintain a normal heart rhythm and improve blood flow to the heart, but human studies are lacking.

3) May Promote Liver Regeneration

People who receive liver transplants often have to take immune-suppressing drugs to prevent transplant rejection, but these drugs reduce the liver’s ability to regenerate. In rats, uridine improved liver regeneration after liver transplants. It completely restored normal liver growth [20].

Over short periods of time, uridine prevents liver damage from drugs in animals. It seems to work as a “salvage” supplement that increases regeneration in times of high stress. The body uses it as a building block for DNA, RNA, and other important molecules [21].

However, chronic uridine supplementation may be harmful. In mice, uridine given to animals over a long period of time worsened liver health and triggered insulin resistance [21].

No studies to date have looked at the effects of uridine on liver health in humans.

Uridine might improve liver regeneration in the short term, but it may harm the liver in the long run. Its effects on liver health in humans are still unknown.

4) May Relieve Depression & 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 [22].

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 [23].

Also, in rats, uridine in combination with omega-3 fatty acids relieved symptoms of depression [24].

Uridine may help relieve depression and bipolar disorder by improving mitochondrial function and cell membrane health.

5) May Help with HIV-Related Problems

According to one study, HIV-positive patients have lower uridine levels in their blood than healthy people do [25].

HIV-positive patients must take antiretroviral medications to control the infection. Over the long term, these drugs cause distressing fat loss in the face, arms, buttocks, and legs [26].

In 165 HIV-infected patients, 24 weeks of uridine supplementation increased fat in the limbs. However, the effect wore off after 1 year. Stronger doses may have been required. Alternately, the patients may simply have been exposed to antiretroviral drugs for too long [26].

Long-term antiretroviral therapy is toxic to the mitochondria. One human study found uridine protected against mitochondrial toxicity from antiretrovirals. Several cell studies support this conclusion [27, 28].

Blood uridine is lower in patients with HIV. Supplementation may help prevent mitochondrial toxicity and fat loss from anti-HIV drugs, but more clinical trials are needed.

6) Improves Lung Diseases

Cystic fibrosis is a genetic disorder in which the lungs become damaged, producing a layer of sticky, persistent mucus that makes breathing a struggle.

In 14 patients with cystic fibrosis, uridine triphosphate (UTP) and the drug amiloride improved breathing and cleared mucus; neither UTP nor amiloride alone significantly improved symptoms, while the combination restored lung function to almost normal levels [29].

Likewise, uridine triphosphate in combination with sodium channel blockers relieved cystic fibrosis symptoms in mice [30].

Uridine furthermore helped clear mucus in healthy people, in 15 patients with chronic mild bronchitis, and in 12 patients with primary ciliary dyskinesia (PCD), a genetic disease that prevents normal airway clearance [31, 32, 33].

Uridine reduced inflammation and scarring in both animal and human cells. In the lungs of mice, it inhibited collagen and TGF-ß synthesis, thereby preventing the growth of scar tissue [34].

Uridine can reduce airway mucus and make it easier to breathe. In small clinical trials, it improved the symptoms of lung diseases such as cystic fibrosis and bronchitis.

7) Reduces Nerve Pain & Damage

In 212 people with peripheral neuropathy, a combination of uridine, folic acid, and vitamin B12 significantly lowered both the intensity of pain and the number of areas affected [35].

Another trial of 48 people suffering from carpal tunnel syndrome confirmed this finding: a similar combination lowered the intensity of the pain by about 40% [35].

In a trial of 400 people, the combination of vitamin B12, uridine, and cytidine effectively reduced nerve pain with only mild side effects. The combination worked better than vitamin B12 alone [36].

Uridine also improved nerve health in 20 patients with diabetic neuropathy, long-term damage to the nerves from high blood sugar [37].

Uridine, especially in combination with vitamin B12, significantly reduces nerve pain. It may also improve nerve health in people with chronic nerve damage.

8) Treats Dry Eyes

Dry eye syndrome, which affects up to 20% of adults, causes low production of tears and inflammation of the eye surface. Oral uridine supplements effectively restored the production of tears in a clinical trial of 27 people with dry eyes [38].

9) May Improve Sleep

Uridine is normally found in breast milk. In 30 infants with disordered sleep, a cereal enriched with uridine-5′-phosphate, tryptophan, and adenosine-5′-phosphate improved sleep quality. When the infants ate the enriched cereal before bedtime, they were much more likely to sleep through the night [39, 40].

Uridine monophosphate (UMP) is recognized as a potential sleep aid in adults, but more research is required to confirm its usefulness. In rats, uridine promotes slow-wave (deep) sleep, which is the most restorative phase of sleep [41, 4].

Uridine Side Effects & Safety

Side Effects

In one clinical trial, uridine caused no side effects over one week in nine healthy people who received it. One person lost consciousness, which, according to the researchers, may not have been from the uridine supplements [7].

In depressed adolescents, uridine side effects were mild and included vivid dreams, abdominal cramps, nausea, diarrhea, and indigestion [22].

According to one review, high doses of uridine can also cause fever in humans [4].

Health Risks

1) Cancer

Uridine supplements may increase cancer risk by activating the P2Y2 receptor. P2Y2 activation is good for autoimmune conditions but may increase the growth of cancers. Several cell studies have shown that activating P2Y2 increases the spread of cancer in both human and animal cells [42, 43, 44, 45, 46].

One possible way that uridine may cause cancer is by incorporating a uracil nucleotide into DNA instead of thymine [47, 48]. Folate and B12 deficiency can cause the same issue. If this is the case, then adequate folate and vitamin B-12 should help counteract uridine’s carcinogenic potential [49, 50].

2) Heart Scarring

In rats, uridine triphosphate (UTP) induced heart tissue scarring (by activating P2Y2 receptors). Scarring thickens the heart’s valves, making the heart muscle less efficient at pumping blood. Scarring that affects a large area of the heart can lead to heart failure [51].

3) Insulin Resistance

In a human trial, patients with type 2 diabetes had higher concentrations of uridine than healthy people. High uridine levels point to insulin resistance as they were linked with high insulin, C-peptide, and HOMA-IR levels [52].

In rats, large doses of uridine infused into the blood caused insulin resistance. Uridine was also shown to increase insulin secretion in human cells [52, 53].

4) Decreased Bone Density

Uridine triphosphate (UTP) may decrease bone density, but the evidence is conflicting. In one study, UTP strongly inhibited bone mineralization and bone formation (via activation of the P2Y2 receptors) [54, 55].

In another study, uridine triphosphate prevented bone building and increased fat cells in the bone marrow, which in turn reduces bone strength [56].

However, a different cell study found uridine triphosphate promoted bone mineralization [57].

There is conflicting evidence of whether uridine promotes bone loss or bone building. If you have osteoporosis or are at risk of developing it, it is probably best to avoid uridine for now.

Uridine Sources, Dosage & Stacks

Food Sources

Babies, who need lots of uridine to support their growing brains, get plenty of this nutrient from breast milk. For the rest of us, some of the food sources richest in uridine include [58, 59, 60]:

Note: according to one old study, uridine in the RNA form in food is not bioavailable. It is completely degraded by the gastrointestinal tract and the liver. If you have a high need for this nutrient, consider using supplements instead of food sources [61].

Dosage

The uridine dosage in clinical trials varied from 1g/day in depressed adolescents to 2g/day in healthy adults. This amount can be split into two or three doses during the day [22, 7].

In adolescents, uridine was given for up to 6 weeks. Healthy volunteers took it for only one week [22, 7].

Studies in cancer patients used very high doses through an IV, adjusted to each person’s weight [62, 63].

We don’t recommend taking uridine over extended periods of time due to the safety concerns linked to its long-term use in animals.

Most supplements contain 200-350 mg/capsule, usually as uridine monophosphate (UMP).

Stacks & Synergies

Lion’s mane & Other Mushrooms

There’s been a lot of talk about stacking uridine with lion’s mane and other medicinal mushrooms. Certain medicinal mushrooms may have unique synergistic effects with uridine, though their combinations haven’t been verified in clinical trials.

Some medicinal mushrooms even contain uridine. Giant oyster mushroom (Pleurotus giganteus) grows wild in Malaysia. Indigenous people of Peninsular Malaysia traditionally use it in cooking. Only recently have researchers discovered that this mushroom is a rich source of uridine and other antioxidants that improve brain health [64, 65].

Specifically, giant oyster mushroom, lion’s mane, and tiger’s milk mushroom (a less known variety) all increase neurite outgrowth, which regenerates nerve cells. They also increased nerve growth factor (NGF) in cells and animals. NGF is a neurotrophic factor that acts as brain food (neuro=brain, trophic=food) [65].

Whether or not lion’s mane also contains uridine is unknown, but this mushroom is certainly a nootropic superfood. Read about its benefits in this post.

Alpha-GPC & Other Brain Nutrients

Alpha-GPC is a supplement that supplies choline and increases acetylcholine levels–the most important neurotransmitter for memory and learning [5].

Theoretically, uridine may enhance the effects of alpha-GPC. The pathway that creates brain phospholipids – including phosphocholine and CDP-choline – needs both choline and uridine in high enough amounts [5].

For the same reason, uridine is sometimes stacked with choline or CDP-choline. Indeed, one study combined uridine with the omega-3 fatty acid DHA and regular choline for increasing brain synapses in animals.

Dopamine-Increasing Supplements

People stack uridine with dopamine-boosting natural substances to enhance focus and motivation. These combinations don’t have clinical-grade data to back them up, but research does support the role of dopamine in attention, motivation, and creativity.

Vitamin B12 & Folate

The following combination was used over 60 days for reducing nerve pain in a clinical study [66]:

  • Uridine monophosphate (UMP) at 50 mg/day
  • Vitamin B12 at 3 mcg/day
  • Folic acid at 400mcg/day

Buy Uridine Supplements

Want More Targeted Ways to Enhance Mood and Brain Function?

If you’re interested in natural and more targeted ways of improving your cognitive function, we recommend checking out the Limitless Mind DNA protocol. It gives genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

If you’re interested in natural and more targeted ways of improving your mood, check out this mood DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help improve your mood.

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About the Author

Jimmy Julajak, MSc

MS (Psychology)

Jimmy got his MSc from the University of Copenhagen.

Jimmy is a psychologist and researcher. He is particularly interested in the workings of the brain and strategies for improving brain health. He believes that people shouldn't hand over the responsibility for their health only to their doctors. His aim is to empower each person with easy-to-understand, science-based health knowledge.

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