Uridine - A Multifaceted Brain Booster

What is Uridine?

A largely unknown dietary supplemented nutrient known as 'Uridine'. Fish may be known as "Food of brain" or "Brain Food" due to presence of this essential nutrient. Also, uridine is a brain vitamin that comes from beer and also present in brewer's yeast; known for its health benefits.

Uridine occurs naturally after being produced by liver. It is one of the five nucleoside that constitute nucleic acid and  is a very important part of RNA (Ribonucleic Acid).  RNA along with DNA (Deoxyribonucleic acid) helps to control the expression of genes.  Hence, it has a vital role in genetic composition also. Moreover, uridine is the indispensable part of basic cell structure of nucleus. Uridine helps in metabolism regulation by creating three nucleotides by substrate of uridine which helps in production of phospholipids found in brain. Chemically, it is glycosylated pyrimidine analog containing uracil which is attached to ribose ring by glycoside bond. Hence, uridine can be defined as a ribonucleioside composed of ribose and uracil. From medicine point of view, it is a white odorless powder which is the nucleoside of uracil possessing and important role in carbohydrate metabolism. Along with it its primary role is  in the functioning of Central Nervous System. It is cholinergic supplement.

How is Uridine synthesized?

In the form of Uridine Monophosphate (UMP), uridine is synthesized in adult liver and is secret in blood. In the bloodstream, it serves multiple purposes including cell rejuvenation. The other forms of uridine found in the bloodstream are uridine triphosphate or uridine 5’monophosphate.

How does uridine work?

Uridine works in many ways. Being, a precursor of brain synapses and nerve cell membrane phospholipids. It enhances cholinergic functions of brain, support the function of liver and mitochondria. Recent researches states that following is the ways suggestive of working of uridine.

 1.Regulation of phosphatidylcholine synthesis

 The main function of uridine are regulation of phosphatidylcholine synthesis which has an impact on memory, cellular structure and lipolysis.

Uridine increases production of phosphatidylcholine in brain which is responsible for regulation of enzymes and cell operations in brain. This in turn, increases synthesis of neuritis which further increases synaptic plasticity(brain’s ability for formation of new memories and neural networks) . Moreover, helps improvement in strong and encoding of memories.

Higher synaptogenesis (formation of nerve synapses which is one of the hallmark of brain development) due to higher uridine levels results in improved memory and stronger cognitive capability.

2.Increase dopamine in brain

Dopamine is one of essential neurotransmitter that works in brain’s pleasure center. Uridine increases the level of dopamine which further is responsible for an individual ability to focus and react to stimuli. It also helps in drive and enhance mood of an individual.

3. Increases choline

. Uridine is converted to CDP choline within brain which increases production of a specific chemical . This chemical is known as Acetylcholine . Acetylcholine is responsible for memory of brain and plasticity of synapses . Hence , It helps in logical thinking , calculations , encoding information and storage of memories. Thus, choline helps to improve synaptic functioning , promote overall health of brain and cardio-protective qualities .

Hence , uridine supports cognition , memory , mood , protects the brain and growth of synapses .

4. Galactose glycolysis pathway

Uridine has a vital role in a pathway which gives energy in the form of glucose. In galactose glycolysis pathway the end product is UDP galactose and glucose 1 phosphate and is processed by enzyme galactose 1 phosphate uridyl transferase (an enzyme formed by uridine).

 

What are the sources of uridine?

Food rich in RNA is considered to be good sources of uridine. A number of foods available everyday are rich in uridine as mentioned below.

-Beer

-Breast milk

-Liver of pig and beef

- Pancreas of pig and beef

-Lymph nodes of beef

-Barley

-Sugarcane

-Fish

-Baker’s yeast

-Mushrooms

-Broccoli

-Oats

-Chinese cabbage

-Spinach

-Cauliflower

-Tomatoes

-Parsley

Regular consumption of above mentioned foods ensures body’s uridine level remains constant.

 

What are the benefits of uridine?

1. Improves Memory

Studies have shown that uridine long term exposure helps in increasing memory in both rats and humans.  Also , Intake of uridine along with choline improves verbal and logical memory.

Deficiency in synapses within the hippocampus and related brain region may think to result Alzheimer's disease (AD ) . The study says administration of three essential nutrient- uridines , omega-fatty acid and docosahexamine acid (DHA ) and choline increases synthesis of new dendritic spine and synapse . This provides restoration with for synapses and improves memory . The function of uridine to stimulate synapse formation helps in delaying symptoms of Alzheimer's disease . In a study conducted on rats , there was increased dopamine and acetylcholine with administration of uridine 5'monophosphate . This increase helped in learning and memory skills improvement in rats . It may be said that , uridine may be helpful only in mild Alzheimer's .

 Uridine increases neuritis formation of brain , results in greater plasticity , better learning and capacity to adapt .

2. Brain Protection and Growth

Brain being the most vital part of functioning as Central nervous system in humans. Studies have shown uridine helped to improve sleep, promote plasticity (change of brain structure and function) and prevents epilepsy. In sleep deprived rats, uridine helped increase slow wave sleep. Also , uridine stopped epileptic episodes of rats . Moreover , neurite filaments and neurites increased in brain cells having improved brain plasticity in rats . Combination of three nutrients that is uridine , DNA and choline helps in increasing the number of synaptic formation in brain . Recent study of 2017 on rat model of hyperoxic induced brain injury states that administration of uridine during course of hyperoxic insult enhances cognitive functions of periadolescent period and helps in prevention of hypo myelination during neonatal periods . Animal models and human studies may state that uridine increases brain levels of ATP (Adenosine Triphosphate ) energy molecules and enhance energy production of circulating glucose . Thus , having a bioenergetic effect . Also , uridine improves brain energy utilization as entering in the brain . Hence , uridine plays an important role in energy pathway by brain cells to maintain ATP production of restricted oxygen conditions . Thus, naturally occurring uridine is a mental stimulant that enhances activity of brain . It is used to improve memory ; synthesis of both old and new memories in the brain . Many studies have named it as miracle drug due to its capability in reversing brain age and improving its intellectual powers .

3. Reduce pain and inflammation

Studies have shown significant effect on pain score as well as intensity of symptoms of patients suffering from carpal tunnel syndrome, when they took a daily capsule of uridine monophosphate and folic acid. Also, uridine triphosphate with folic acid and cytidine helped in reducing back, neck and hip pain in humans. Hence, uridine reduces inflammation and promotes positive muscle strength. Moreover, uridine  drug is often used by athletes to get away with muscle problems.

Uridine also showed anti-inflammatory effect oh human lung cells.

4. Protect the heart

In a study done on rats , there was increased blood supply (during course of inadequate blood supply and oxygen ) with administration of both uridine and uridine 5'monophosphate . Furthermore , normalize the heart and stabilize heart rhythm . A study conducted on rats states that uridine triphosphate initiates profibrotic response to from cardiac fibroblasts (play a key role in response to injury and remodeling ) . Hence , Heart contractions can be decreased from to heart attacks by uridine triphosphate .

Moreover, It can be said that uridine improves the health of heart and helps in reduction of heart failure.

5. Restore liver Growth

After liver  transplantation in rats, uridine has helped in growth of  liver and liver cell. Hence, restoring liver regeneration.

6. Reduce liver lipid accumulation

  It has been proven that there is drug induced liver lipid accumulation known as Fatty liver. But, studies have shown that short term co-administration of uridine with other drugs may prevent fatty liver.

7. Treatment of depression and  bipolar disorders

Uridine decreases symptoms of depression in rats. Treatment of uridine has helped in prevention of depression symptoms of adolescent humans.

In a study done on rats there may be antidepressant effect of on administration of uridine and omega 3 fatty acids.These two substances are commonly present in food such as fish, walnuts, molasses and sugar beets. Therefore, when omega 3 fatty acid taken with uridine enhances antidepressant effect.

Mitochondrial dysfunction may be one of the factors influencing bipolar disorders. Uridine has helped from prevention of problems with mitochondria in human cells.

8. Role of supplementation of uridine in HIV related problems

Studies have shown HIV positive patients have a lower uridine level in their blood as compared to healthy patients. Abnormal loss of fat in parts of the body known as lipoatrophy occurs to HIV positive patients. A study done on HIV patients has had shown increase in limb fat with administration of uridine supplementation for 24 weeks. However, the same effect may not have been shown  after 48 weeks that may be due to dose of uridine and does not indicate that there is no beneficial effect of uridine. Also, long term antiretroviral therapy used in treatment of HIV results in mitochondrial dysfunction in human patients cells and cause toxicity. Supplementation of uridine can reverse these effects.

9. Helps in Cystic fibrosis treatment

The genetic disorder that can damage the digestive system and lungs is known as cystic fibrosis. In this there is increased secretions in lungs due to sodium absorption, which may further cause breathing problems. CI secretions increased by uridine thicken the secretions in the lungs, helps in mucus easier to get rid of. In a study administration of sodium channel blocker  with uridine triphosphate, have shown to relieve of cystic fibrosis in mice.

In adult, human cystic fibrosis may be  treated with uridine 5’ triphosphate and amiloride being helpful in enhancing airway and to clear the mucus.

10. Help in Anemia

The combination of uridine, vitamin B 12 and cytidine helped in treatment of symptoms of anemia in population studied in double blind trial.

11. Increase motivation levels and intelligence

Uridine leads to increase in mood and overall motivation level. It has a control on cortisol secretion thereby reducing anxiety and stress. Hence, it reduces stress, anxiety and reduction of symptoms of obsessive compulsive disorders (OCD).

Some studies suggest that uridine has positive effect on fluid intelligence which is a predictor of intellectual capacity than IQ intelligence.

Adverse effects of uridine

Studies have shown uridine milder side effects of supplement which occur often to 30 minutes of consumption is fever, diarrhea and may induce palpitations. Some of the specific adverse effects which may occur after taking high dose are listed below:-

A. Cancer

Uridine consumption of pharmacological form can be carcinogenic. According to the studies, the activation of P2Y2 receptor by uridine triphosphate which increases the spread of human pancreatic cancer cells in vitro. Uridine can increase liver cancer in cell model. Also, another mechanism which helps uridine cause cancer by replacing uracil by thymine in DNA.

Activation of antitumor prodrugs in human cancer cells shows increased uridine cytidine kinase 2(UCK 2 an enzyme that is involved in pathway of nucleotide biosynthesis) and suggest that UCK 2 may be a prognostic biomarker for patients with breast cancer.

Invasion of breast cells increased by UDP(uridine diphosphate) in breast cell metastasis mouse model and in human breast cells. Therefore, it may suggest that treatment of cancer (by chemotherapy) induces uridine diphosphate release to promote breast cancer.

B. Heart diseases

Uridine triphosphate in rats causes cardiac fibroblast responses by activating P2Y2 receptors. Thickening of heart valves (fibrosis) may lead to failure of heart.

C. Insulin resistance

Uridine infused into with large amount of blood of rats cause insulin resistance. There is higher concentration of uridine in diabetic patients as compared to healthy patients.

There is increased insulin secretion by uridine diphosphate and uridine triphosphate in human cells.

D. Inhibit bone formation

Low concentration of uridine triphosphate inhibits bone mineralization and formation by P2Y2 receptor. Also, it increases adipogenesis and prevents osteogenesis.

RNA rich food may lead to high level of purines (adenine and guanosine) in blood. That in return increases uric acid production and may lead to gout (inflammatory arthritis especially of base of big toe joint) and may lead to kidney stones or urate neuropathy.

E. Fatty liver and Pre-diabetic condition

Studies done on short term co-administration of uridine with other drugs prevent drug induced liver lipid accumulation. On the other hand, a study done on mice states that long term administration of uridine leads to systemic glucose intolerance and severe liver lipid accumulation. Thus, long term administration of uridine has had shown to lead to fatty liver and condition like pre-diabetes.

Uridine supplements and usage

• Though, uridine is present in various foods. But, at the same time there are many uridine supplements available. It is recommended that these supplements should be taken in dosage of between 50mg and 2g per day. This supplement is usually taken for the purpose pf nootropics(naturally occurring man made chemical that give benefits of cognition to human brain).

A study done on normal adult gerbils has shown improvement in memory and learning with administration of uridine , choline and docosahexaenoic acid (DHA ) . Also , researches recommend that uridine supplements should be taken with choline , omega 3 fatty acids or docosahexaenoic acid (DHA ) for better results .

References

1. Wurtman RJ et al. Synapse formation in brain can be enhanced by co-administering three specific nutrients. Eur J Pharmacol. 2017 Oct;10(5):12-18.
2. Shen G et al. Overexpression of uridine cytidine kinase 2 correlates with breast cancer prognosis and poor prognosis. J Breast cancer, 2017 Jun;20(2):132-141.
3. Max at al. Chemotherapy induced uridine diphosphate release to promote breast cancer metasis through P2Y6 activation. Oncotarget. 2016 May 17;7(20):29036-50.
4. Amante DJ et al. Uridine ameliorates the pathological phenotype in transgenic G93A-ALS. Amyotroph Lateral Scler. 2010 Dec;11(6):520-30.
5. Sarah et al. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gebrils. FASEB J. 2008 Nov;22(11):3938-3946.