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 the body break down sugar for energy. It plays a big role in 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].
- May enhance cognitive function
- May reduce nerve pain
- May protect the mitochondria
- May improve the symptoms of lung diseases
- May help with depression and bipolar disorder
- May improve sleep quality
- Insufficient evidence for all benefits
- Unknown long-term benefits and safety profile
- Not recommended for those with cancer, fibrosis, diabetes, or osteoporosis
Benefits of Uridine
Insufficient Evidence for:
1) Learning & Memory
The 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 .
Uridine creates the right environment for increased neuronal plasticity and synapse formation, which may help 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].
Although promising, most of the effects of uridine on learning and memory have been observed in animals and cells. Clinical research is needed to confirm these preliminary findings.
2) 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 .
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 .
Also, in rats, uridine in combination with omega-3 fatty acids relieved symptoms of depression .
All in all, the evidence to support the role of uridine in improving depression is insufficient. Larger, more robust clinical trials are required.
3) 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 .
Another trial of 48 people suffering from carpal tunnel syndrome seems to confirm this finding: a similar combination lowered the intensity of the pain by about 40% .
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 .
Uridine also improved nerve health in 20 patients with diabetic neuropathy, long-term damage to the nerves from high blood sugar .
Although promising, the evidence to support the benefits of uridine in nerve pain and damage comes from a few clinical trials, most of which tested it in combination with vitamins. More clinical trials using uridine alone are needed to confirm these results.
4) 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 .
Likewise, uridine triphosphate in combination with sodium channel blockers relieved cystic fibrosis symptoms in mice .
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 [25, 26, 27].
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 .
The results are promising, but the evidence to back this use of uridine is insufficient due to the small size of the clinical trials. Further research on larger populations is warranted to confirm their results.
5) HIV-Related Problems
According to one study, HIV-positive patients have lower uridine levels in their blood than healthy people do .
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 .
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 .
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 [31, 32].
Whether uridine effectively helps prevent adverse effects of HIV medication should be confirmed in further clinical trials.
6) 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 small trial of 27 people with dry eyes .
A single clinical trial cannot be considered sufficient evidence to back this use. More studies on larger populations are needed before concluding that uridine helps improve dry eye syndrome.
7) Sleep Aid
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 [34, 35].
Uridine monophosphate (UMP) has been identified 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 [36, 4].
Again, very few studies have investigated the use of uridine as a sleep aid. Further clinical research is needed.
Animal and Cell Research (Lack of Evidence)
Other potential health benefits of uridine are currently being investigated. Because the research is still at the animal and cell stage, we cannot conclude for certain that the effects will be the same in humans.
Protecting the Heart
When the heart doesn’t get enough oxygen, it may suffer damage. The arteries supplying the heart are usually either partially or completely blocked, most commonly due to fatty plaques .
In a rat study, uridine normalized the heart’s rhythm by reactivating energy metabolism. It was most effective as uridine-5′-monophosphate (UMP) .
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 .
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 .
Over short periods of time, uridine prevented 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 .
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 .
No studies to date have looked at the effects of uridine on liver health in humans.
Uridine Side Effects & Safety
Keep in mind that the safety profile of uridine is relatively unknown, given the scarcity of well-designed clinical studies. The list of side effects below is, therefore, not a definite one. You should consult your doctor about other potential side effects based on your health condition and possible drug or supplement interactions.
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 .
In depressed adolescents, uridine side effects were mild and included vivid dreams, abdominal cramps, nausea, diarrhea, and indigestion .
According to one review, high doses of uridine can also cause fever in humans .
Preliminary research has associated high uridine levels or intake with some health conditions. Most of it was conducted in animals and cells, which means uridine may not have the same effects in humans. The only human study was a cohort study. While it associated high blood uridine levels with insulin resistance, it couldn’t establish it as its cause.
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 .
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 .
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 in cells, UTP strongly inhibited bone mineralization and bone formation (via activation of the P2Y2 receptors) [54, 55].
In another cell study, uridine triphosphate prevented bone building and increased fat cells in the bone marrow, which in turn reduces bone strength .
However, a different cell study found uridine triphosphate promoted bone mineralization .
Uridine Sources, Dosage & Stacks
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]:
- Nutritional yeast
- Brewer’s yeast
- Some vegetables (e.g. mushrooms, broccoli, oats)
- Organ meat (e.g. liver, pancreas) and fish
Consult with your doctor if increasing your uridine intake may be beneficial in your case before implementing any dietary changes.
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, consult your doctor about using supplements instead of food sources .
Because uridine supplements are not approved for any health conditions, there is no official dose. The unofficial doses are based on the ones used in clinical trials and the experience of both users and supplement manufacturers.
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 [17, 7].
In adolescents, uridine was given for up to 6 weeks. Healthy volunteers took it for only one week [17, 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
Uridine is often stacked with other supplements. However, the evidence supporting the effectiveness of these combinations is limited to non-existent. Supplements are not approved by the FDA for any conditions and regulations set manufacturing standards but don’t guarantee that they’re safe or effective. Talk to your doctor before taking any supplements to avoid potentially dangerous interactions.
Lion’s Mane & Other Mushrooms
There’s been a lot of talk about stacking uridine with lion’s mane and other medicinal mushrooms. Certain mushrooms may have unique synergistic effects with uridine, though their combinations haven’t been verified in clinical trials.
Some 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 may 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) .
Whether or not lion’s mane also contains uridine is unknown, but this mushroom is certainly a food with potential nootropic effects. 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 .
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 .
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.
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 successfully used over 60 days for reducing nerve pain in a clinical study :
- Uridine monophosphate (UMP) at 50 mg/day
- Vitamin B12 at 3 mcg/day
- Folic acid at 400mcg/day