Uridine

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- Uridine -

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Observations:

(Part of the Gerbil Food Cocktail for memory enhancement.)

Wikipedia entries:

Uridine:

Uridine is a molecule (known as a nucleoside) that is formed when uracil is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond.

If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine.
[edit] Dietary sources of uridine

Uridine is one of the four basic components of ribonucleic acid (RNA); the other three are adenosine, guanosine, and cytidine. Upon digestion of foods containing RNA, uridine is released from RNA and is absorbed intact in the gut. Some common food sources of uridine are:

    * Sugarcane extract
    * Tomatoes (0.5 to 1.0 g uridine per kilogram dry weight)
    * Brewer’s yeast (3% uridine by dry weight)
    * Beer
    * Broccoli
    * Organ meats (liver, pancreas, etc.)

Consumption of RNA-rich foods may lead to high levels of purines (adenosine and guanosine) in blood. High levels of purines are known to increase uric acid production and may aggravate or lead to conditions such as gout. Moderate consumption of yeast, about 5 grams per day, should provide adequate uridine for improved health with minimal side effects.[citation needed]

Note: It has been suggested that the RNA content of yeast products should be chemically reduced if these products are to be consumed in high amounts (50 grams or more per day) as a source of protein. However, such processing is expensive and, as of 2008, commonly available brewer's yeast products were not RNA-reduced.[citation needed]

Harvard researchers report that supplementation in rats with a combination of uridine and EPA/DHA omega-3 fatty acids has antidepressant activity equivalent to that of commonly prescribed antidepressant medications, such as Prozac and other SSRIs.[5]
http://en.wikipedia.org/wiki/Uridine

Uridine monophosphate, also known as 5'-uridylic acid and abbreviated UMP, is a nucleotide that is found in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase uracil; hence, it is a ribonucleoside monophosphate. Another common shorthand for the molecule is uridylate - the deprotonated form of the molecule, which is predominant in aqueous solution. As a substituent it takes the form of the prefix uridylyl-...

Uridine Monophosphate in Foods

In brain research studies such as those mentioned in this article, uridine monophosphate is used as a convenient delivery compound for uridine. Uridine is the active ingredient of the compound. A common misconception is that uridine and its compounds are not available in significant quantities from foods and must be obtained from expensive supplements or prescription drugs. This is not so. Uridine monophosphate is a major component of RNA. Any food rich in RNA, such as Brewer's yeast or some organ meats, will provide significant quantities of it. For more information, consult the article on uridine.

http://en.wikipedia.org/wiki/Uridine_monophosphate

Effect of oral CDP-choline on plasma choline and uridine levels in humans.
Wurtman RJ, Regan M, Ulus I, Yu L.
Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
Twelve mildly hypertensive but otherwise normal fasting subjects received each of four treatments in random order: CDP-choline (citicoline; 500, 2000, and 4000 mg) or a placebo orally at 8:00 a.m. on four different treatment days. Eleven plasma samples from each subject, obtained just prior to treatment (8:00 a.m.) and 1-12 hr thereafter, were assayed for choline, cytidine, and uridine. Fasting terminated at noon with consumption of a light lunch that contained about 100 mg choline. Plasma choline exhibited dose-related increases in peak values and areas under the curves (AUCs), remaining significantly elevated, after each of the three doses, for 5, 8, and 10 hr, respectively. Plasma uridine was elevated significantly for 5-6 hr after all three doses, increasing by as much as 70-90% after the 500 mg dose, and by 100-120% after the 2000 mg dose. No further increase was noted when the dose was raised from 2000 to 4000 mg. Plasma cytidine was not reliably detectable, since it was less than twice blank, or less than 100 nM, at all of the doses. Uridine is known to enter the brain and to be converted to UTP; moreover, we found that uridine was converted directly to CTP in neuron-derived PC-12 cells. Hence, it seems likely that the circulating substrates through which oral citicoline increases membrane phosphatide synthesis in the brains of humans involve uridine and choline, and not cytidine and choline as in rats.
PMID: 10974208 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/10974208

Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats.
Wang L, Pooler AM, Albrecht MA, Wurtman RJ.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
J Mol Neurosci. 2005;27(1):137-45.

Abstract

Membrane phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by cellular levels of its precursor, cytidine-5'-diphosphate choline (CDP-choline), which is produced from cytidine triphosphate (CTP) and phosphocholine. In rat PC12 cells exogenous uridine was shown to elevate intracellular CDP-choline levels, by promoting the synthesis of uridine triphosphate (UTP), which was partly converted to CTP. In such cells uridine also enhanced the neurite outgrowth produced by nerve growth factor (NGF). The present study assessed the effect of dietary supplementation with uridine-5'-monophosphate disodium (UMP-2Na+, an additive in infant milk formulas) on striatal dopamine (DA) release in aged rats. Male Fischer 344 rats consumed either a control diet or one fortified with 2.5% UMP for 6 wk, ad libitum. In vivo microdialysis was then used to measure spontaneous and potassium (K+)-evoked DA release in the right striatum. Potassium (K+)-evoked DA 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); basal DA release was unchanged. In general, each animal's K+-evoked DA release correlated with its striatal DA content, measured postmortem. The levels of neurofilament-70 and neurofilament-M proteins, biomarkers of neurite outgrowth, increased to 182+/-25% (p<0.05) and 221+/-34% (p<0.01) of control values, respectively, with UMP consumption. Hence, UMP treatment not only enhances membrane phosphatide production but also can modulate two membrane-dependent processes, neurotransmitter release and neurite outgrowth, in vivo.
PMID: 16055952 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16055952

Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils.
Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, E25-604, MIT, Cambridge, MA 02139, USA.
Brain Res. 2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29.

Abstract

We examined the biochemical pathways whereby oral uridine-5'-monophosphate (UMP) increases membrane phosphatide synthesis in brains of gerbils. We previously showed that supplementing PC12 cells with uridine caused concentration-related increases in CDP-choline levels, and that this effect was mediated by elevations in intracellular uridine triphosphate (UTP) and cytidine triphosphate (CTP). In the present study, adult gerbils received UMP (1 mmol/kg), a constituent of human breast milk and infant formulas, by gavage, and plasma samples and brains were collected for assay between 5 min and 8 h thereafter. Thirty minutes after gavage, plasma uridine levels were increased from 6.6 +/- 0.58 to 32.7 +/- 1.85 microM (P < 0.001), and brain uridine from 22.6 +/- 2.9 to 89.1 +/- 8.82 pmol/mg tissue (P < 0.001). UMP also significantly increased plasma and brain cytidine levels; however, both basally and following UMP, these levels were much lower than those of uridine. Brain UTP, CTP, and CDP-choline were all elevated 15 min after UMP (from 254 +/- 31.9 to 417 +/- 50.2, [P < 0.05]; 56.8 +/- 1.8 to 71.7 +/- 1.8, [P < 0.001]; and 11.3 +/- 0.5 to 16.4 +/- 1, [P < 0.001] pmol/mg tissue, respectively), returning to basal levels after 20 and 30 min. The smallest UMP dose that significantly increased brain CDP-choline was 0.05 mmol/kg. These results show that oral UMP, a uridine source, enhances the synthesis of CDP-choline, the immediate precursor of PC, in gerbil brain.

PMID: 16126180 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16126180

The effect of RNA supplementation of rat diets on the composition of body fluids.
Heaf DJ, Davies JI.
Br J Nutr. 1976 Nov;36(3):381-402.

Abstract

1. In a number of separate experiments, yeast RNA, mixtures of its constituent nucleosides, its constituent bases and ribose were administered orally to rats. In each instance, the resultant changes in the composition of body fluids were monitored using sensitive methods. 2. Ingestion of RNA (100 g/kg diet) caused detectable increases in intestinal ribose, inorganic phosphate, uridine, pseudouridine, uracil, inosine, uric acid and probably other purine bases. Their accumulation did not detectably affect the rate of passage of food along the digestive tract, even though some nucleosides are known to affect gut motility. 3. Although plasma levels of uric acid and uridine were higher when RNA was administered in the diet, these changes were very slight compared with those in plasma uracil, which in some experiments were increased more than 20-fold compared with control levels (300 mumol/l). Analysis of erythrocytes indicated that the internal environment of at least some cells of the body are similarly altered. 4. Analyses indicated that all dietary RNA-phosphate passed into the urine from the gut but most of the RNA-ribose was probably metabolized. Uracil and uric acid levels in the urine reflected plasma composition. 5. The effect of orally administered mixed nucleosides on blood and urine composition was similar to that of RNA, but the response to an equivalent mixture of free bases differed in several respects; cytosine, adenine and hypoxanthine appeared in urine only under these circumstances.

PMID: 795459 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/795459

Effect of beer on the plasma concentrations of uridine and purine bases.
Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Fukuchi M, Hada T.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Metabolism. 2002 Oct;51(10):1317-23.

Abstract

We conducted the present study to determine whether beer, both with and without ethanol content, increases the plasma concentration and urinary excretion of purine bases and uridine. Because 10 mL of regular beer (with ethanol) was found to contain 0.34 g of freeze-dried beer (without ethanol) and 0.5 mg of uridine, 5 healthy males were given regular beer (10 mL/kg of body weight) and freeze-dried beer (0.34 g/kg of body weight) or uridine (0.5 mg/kg of body weight). The plasma concentrations of hypoxanthine, xanthine, and uridine increased by 3.5-fold (P <.05), 4.7-fold (P <.05), and 1.8-fold (P <.05), respectively, 30 minutes after regular beer ingestion, and the urinary excretion of hypoxanthine, xanthine, and uridine increased by 4.0-fold (P <.05), 4.5-fold (P <.01), and 1.7-fold (P <.05), respectively, when measured 1 hour after ingestion. The plasma concentrations of uric acid and total purine bases increased by 6.5% (P <.05) and 7.6% (P <.05), respectively, 30 minutes after regular beer ingestion, whereas the urinary excretion of uric acid did not increase, while that of total purine bases increased by 1.3-fold (P <.05) when measured 1 hour after ingestion. As for freeze-dried beer, the plasma concentrations of uric acid total purine bases increased by 4.4% (P <.05) and 4.6% (P <.05), respectively, and that of uridine by 1.5-fold (P <.01) 30 minutes after ingestion, while the urinary excretion of uridine increased by 1.4-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine and xanthine and the urinary excretion of uric acid and total purine bases did not change significantly. As for uridine ingestion, the plasma concentration of uridine increased by 1.37-fold (P <.01) 30 minutes after ingestion, and the urinary excretion of uridine increased by 1.3-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine, xanthine, uric acid, and total purine bases did not change significantly. These results suggest that the purines in beer played a major role in the increase in the plasma concentration of uric acid, while both uridine and ethanol in beer had a significant effect on the increase in plasma concentration of uridine.

PMID: 12370853 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/12370853

Effect of oral CDP-choline on plasma choline and uridine levels in humans.
Wurtman RJ, Regan M, Ulus I, Yu L.
Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
Abstract
Twelve mildly hypertensive but otherwise normal fasting subjects received each of four treatments in random order: CDP-choline (citicoline; 500, 2000, and 4000 mg) or a placebo orally at 8:00 a.m. on four different treatment days. Eleven plasma samples from each subject, obtained just prior to treatment (8:00 a.m.) and 1-12 hr thereafter, were assayed for choline, cytidine, and uridine. Fasting terminated at noon with consumption of a light lunch that contained about 100 mg choline. Plasma choline exhibited dose-related increases in peak values and areas under the curves (AUCs), remaining significantly elevated, after each of the three doses, for 5, 8, and 10 hr, respectively. Plasma uridine was elevated significantly for 5-6 hr after all three doses, increasing by as much as 70-90% after the 500 mg dose, and by 100-120% after the 2000 mg dose. No further increase was noted when the dose was raised from 2000 to 4000 mg. Plasma cytidine was not reliably detectable, since it was less than twice blank, or less than 100 nM, at all of the doses. Uridine is known to enter the brain and to be converted to UTP; moreover, we found that uridine was converted directly to CTP in neuron-derived PC-12 cells. Hence, it seems likely that the circulating substrates through which oral citicoline increases membrane phosphatide synthesis in the brains of humans involve uridine and choline, and not cytidine and choline as in rats.
PMID: 10974208 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/10974208

Tesla: Effects of Triacetyluridine (TAU) in the treatment of mood disorders
Brain 31P-MRS at 4.0
J. E. Jensen1, F. Hirashima1, B. M. Cohen1, A. L. Stoll1, B. D. Frederic1, P. F. Renshaw1
1Brain Imaging Center, McLean Hospital, Belmont, Massachusetts, United States
http://cds.ismrm.org/ismrm-2004/Files/001482.pdf

Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement
Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement.
Weinberg ME, Roman MC, Jacob P, Wen M, Cheung P, et al.
PLoS ONE 6(2): e14709. doi:10.1371/journal.pone.0014709 (2011)
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014709

Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.
PLoS One. 2011 Feb 17;6(2):e14709.
Weinberg ME, Roman MC, Jacob P, Wen M, Cheung P, Walker UA, Mulligan K, Schambelan M.
Abstract
BACKGROUND:

Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels.
METHODOLOGY/PRINCIPAL FINDINGS:

Single- and multi-dose PK studies following NucleomaxX® were compared to single-dose PK studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than 90% of the nucleoside component of NucleomaxX® is in the form of triacetyluridine (TAU). Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max) and AUC were four-fold higher after a single dose of NucleomaxX® than after uridine. No adverse effects of either treatment were observed.
CONCLUSIONS/SIGNIFICANCE:

NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.
http://www.ncbi.nlm.nih.gov/pubmed/21379380

Nutrient mixture improves memory in patients with early Alzheimer’s
In clinical trial, mixture developed at MIT appears to help overcome loss of connections between brain cells.
Anne Trafton, MIT News Office
July 9, 2012
… Wurtman came up with a mixture of three naturally occurring dietary compounds: choline, uridine and the omega-3 fatty acid DHA. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine is produced by the liver and kidney, and is present in some foods as a component of RNA…. Results of the clinical trial, conducted in Europe, appear in the July 10 online edition of the Journal of Alzheimer’s Disease…
http://web.mit.edu/newsoffice/2012/alzheimers-nutrient-mixture-0709.html

[Problem is finding uridine in bulk or supplement. Is used in infant formula, so it must be available in 55-gallon drums, but no luck finding it cheap in capsules.]

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients.
Jensen JE, Daniels M, Haws C, Bolo NR, Lyoo IK, Yoon SJ, Cohen BM, Stoll AL, Rusche JR, Renshaw PF.
Exp Clin Psychopharmacol. 2008 Jun;16(3):199-206.
Source: Brain Imaging Center, McLean Hospital, Belmont, Massachusetts 02478-9106, USA.
Abstract
Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.
PMID: 18540779 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/18540779

http://www.ninds.nih.gov/research/parkinsonsweb/cinaps/Compound%20Dossiers/Triacetyluridine%20dossier.pdf

TAU:

Neuroprotective effects of oral administration of triacetyluridine against MPTP neurotoxicity.
Klivenyi P, Gardian G, Calingasan NY, Yang L, von Borstel R, Saydoff J, Browne SE, Beal MF.
Neuromolecular Med. 2004;6(2-3):87-92.
Source: Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York-Presbyterian Hospital, New York, NY, USA.
Abstract
Administration of triacetyluridine (TAU) is a means of delivering exogenous pyrimidines to the brain, which may help to compensate for bioenergetic defects. TAU has previously been shown to be neuroprotective in animal models of Huntington's and Alzheimer's diseases. We examined whether oral administration of TAU in the diet could exert significant neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity model of Parkinson's disease. Administration of TAU significantly attenuated MPTP-induced depletion of striatal dopamine and loss of tyrosine-hydroxylase-positive neurons in the substantia nigra. These findings suggest that administration of TAU may be a novel approach for treating neurodegenerative diseases associated with impaired mitochondrial function.
PMID: 15970626 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/15970626

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Known sources:
Jarrow Formulas UMP(uridine 5'-monophosphate disodium salt) 250mg 60 capsules/bottle http://www.jarrow.com/product/600/Uridine

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Natural sources:

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References:

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