2844 replies to this topic

[MrHappy]

http://www.smart-pub...inst-Alzheimers
Repost from Tham in medicines and diseases (thank you, Tham!)

http://proteom.elte....Curr_Top_11.pdf
Uridine function in the CNS


STICKY:
This sticky is a work in progress. I'm cleaning up this thread and compiling a list of all of the journal articles/links, etc. here, grouped with their issues. Please stand by (I'm up to page 22.)

Caveats: This is a research topic. Substances discussed in this thread are being used in human clinical trials for bipolar disorder, alzheimer's disease and some other ailments. While these trials and >12 months of user-feedback from these forums have been largely successful, this protocol is not yet within the realms of well-trodden medical circles. Proceed at your own risk, preferrably after reading the entire thread.

Uridine promotes cellular growth and DNA repair. By virtue of this, it can accelerate the effects of a folate (Vitamin B9) deficiency.

Folate deficiency can lead to DNA transcription errors, strand breakage and carcinogenesis. Conversely, too much folate can also cause the same issues.
http://jn.nutrition....127/5/834S.full
Dietary Nucleotides: Effects on Cell Proliferation Following Partial Hepatectomy in Rats Fed NIH-31, AIN-76A, or Folate/Methyl-Deficient Diets1

http://bloodjournal....6/1656.full.pdf
Bone Marrow Cells from Vitamin B12 and Folate-Deficient Patients Misincorporate Uracil Into DNA

http://www.ncbi.nlm..../pubmed/4077052
Human chromosome hot points. IV. Uridine-induced hot-point breaks at 3p14 and 16q23-24 and increased expression of fragile site Xq27 in folate-free medium

http://onlinelibrary....x/abstract#fn1
Deranged DNA Synthesis by Bone Marrow from Vitamin B12-Deficient Humans

Obtaining the RDA for B group vitamins from food or supplements should be part of any normal daily regimen, but if you are going to take uridine, it is a suggested requirement to take a multi-B vitamin with it, regardless of your diet.

Benefits reported for -
Uplifting and stabilising mood
Stress
OCD
Anxiety
Modulating / normalising dopamine release
http://www.ncbi.nlm....pubmed/15705349
Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.

http://cat.inist.fr/...cpsidt=17035532
Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats

http://ebm.rsmjourna...4/1/49.abstract
Chronic uridine modulates the stimulant-induced release of dopamine

http://wurtmanlab.mi...ic/pdf/1034.pdf
Restorative effects of uridine plus docosahexaenoaic in in a rat model of Parkinson' disease

http://docs.docstoc....a223d245da5.pdf
Effect of chronical treatment with uridine on rats per os on immunoreactivity from somatistatin and cholecystokinin (testing methamphetamine and haloperidol)

http://www.ncbi.nlm....ubmed/20504471/
Effects of chronic treatment with uridine on striatal dopamine release and dopamine related behaviours in the absence or the presence of chronic treatment with haloperidol.

http://cds.ismrm.org...iles/001482.pdf
Brain 31P-MRS at 4.0 Tesla: Effects of Triacetyluridine (TAU) in the treatment of mood disorders

http://www.sciencedi...09130579500169W
Uridine reduces rotation induced by l-Dopa and methamphetamine in 6-OHDA-treated rats

http://www.ncbi.nlm....pubmed/26188642

Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial.

Cellular growth / health and replication
Mitochondrial efficiency
http://www.ncbi.nlm....ubmed/15654852/
Secretion of ATP from Schwann cells in response to uridine triphosphate.

http://www.ncbi.nlm....pubmed/17538545
Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

Sleep / sleeping patterns
http://www.ncbi.nlm....pubmed/11322706
Uridine receptor: discovery and its involvement in sleep mechanism.

Learning and memory
General cognitive decline
Synaptogenesis
Neurogenesis
Myelation
Increasing free phosphatidylcholine
Increasing receptor densities
Improving lipid membrane health
http://www.fasebj.or...1/3938.abstract
Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils

http://www.sciencedi...074742703000248
Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats

http://www.ncbi.nlm....pubmed/17950710
Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus.

http://www.ncbi.nlm....pubmed/18631994
Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses.

http://www.ncbi.nlm....pubmed/17349923
Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid beta and interferon-gamma-induced microglial activation.

http://www.ncbi.nlm....34/?tool=pubmed
Dietary supplementation with uridine-5′-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat

http://www.ncbi.nlm....pubmed/19262950
Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides.

http://www.dementiat...eimers-disease/
Nutritional intervention helps in mild Alzheimer’s disease

http://m.pnas.org/co...4/21/11601.full
Developmental disorder associated with increased cellular nucleotidase activity

http://content.karge...roduktNr=224107
Giving Uridine and/or Docosahexaenoic Acid Orally to Rat Dams during Gestation and Nursing Increases Synaptic Elements in Brains of Weanling Pups

http://www.bbc.co.uk...health-16344228
Alzheimer's: Diet 'can stop brain shrinking'

Bowel flora and fauna
http://ajcn.nutritio.../87/6/1785.full
Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial

Anemia
http://www.moreirajr...id_materia=3707
Efficacy and tolerability of a combination of uridine, cytidine, and vitamin B12 in anemia. A double-blind, comparative study versus nucleotide monotherapy

Cardiovascular health
Neural bloodflow
Antiviral properties
Type-2,3 diabetes (Alzheimers' disease being discussed elsewhere as T3D)
Halting a 5FU chemotherapy overdose and increasing selectivity of 5FU.
NMDA antagonist
AMPA agonist


Recommendations for people just starting out with uridine supplementation
For the first 2 weeks:
150-250mg UMP, orally, twice per day
A *good* multi vitamin, that includes RDA of B-group Vitamins and a broad range of trace minerals, including magnesium
500IU of mixed vitamin E
A large dose of fish oil with >700mg DHA + >300mg EPA (or 3000mg ALA / flaxseed oil, if you are vegetarian)

After 2 weeks:
Slowly introduce choline - start with 50mg of eg.alpha-GPC or CDP-choline and ramp it up to around 300mg.
If you experience depressive symptoms from choline, discontinue choline and consider ALCAR as an alternative.

Finding the optimal dose of uridine for you:
Too little uridine and you likely won't see the benefits for a long time
Too much uridine and you'll likely feel emotionally dull / overly focused.

Sublingual or Oral?:
Sublingual doses are predicted to be around 7x-10x the equivalent oral dose. If you are troubleshooting brainfog, you may benefit from these higher doses. People primarily looking for a mood lift would be advised to start with an oral dose first and make adjustments from there.

Differences between UMP and TAU:
Uridine-5'-Monophosphate (UMP) is water soluble and can be taken sublingually, if higher doses are desired.
Triacetyluridine (TAU) is fat soluble, but 4x-7x stronger, orally, than UMP.
From user reports, UMP appears to be more effective / better value, overall.
UMP is available in bulk powder. TAU is available in capsule form, which is convenient for travelling.

Who SHOULDN'T take uridine:
Over-methylators. If you do not respond well to Vitamin B, or SAMe, you are unlikely to enjoy any benefits from uridine supplementation.
http://www.enzymestu...methylation.htm

People who can't or are unwilling to cut down or eliminate nicotine or caffeine from their diet. Uridine amplifies the effect of these stimulants and others, including methamphetamines. It could be helpful in reducing dependence on these stimulants.

http://molpharm.aspe.../4/925.full.pdf
Interactions of Nucleoside Analogs, Caffeine, and Nicotine with Human Concentrative Nucleoside Transporters 1 and 2 Stably Produced in a Transport-Defective Human Cell Line

http://www.freepaten...06/0217344.html Compounds for the treatment of tobacco dependence and withdrawal

Edited by MrHappy, 22 July 2015 - 10:36 AM.

[nito]

cool where can you get uridine?

[rwac]

The best/cheapest source of uridine is RNA. lef has a decent RNA product.

Other sources of uridine are yeast extract, beer etc.

Edited by rwac, 30 September 2011 - 01:08 AM.

[nito]

brewers yeast?

[rwac]

yup.

[nito]

cool, going to start mixing brewers yeast, alpha gpc/acp choline and DHA, i guess normal fish oil.

[nito]

that link however does not mention how they administered it and in what ratios, and how long it took to get the results. So i am not sure how to approach the trial, i mean i can't just take random dosages everyday.

[MrHappy]

The references section on that page linked to the research papers. Anyone have full text access?

[MrHappy]

Incidenty 25g of uridine for $50 on ebay. 50g of GPC for $50.

[MrHappy]

Here we go
http://www.cholineba...uridine-bo.html

http://www.fasebj.or...1/3938.abstract

[MrHappy]

And more..

http://www.sciencedi...074742703000248

http://www.ncbi.nlm....pubmed/10974208
http://www.ncbi.nlm....pubmed/12737935
http://www.longecity...357#entry325357

RNA here:
http://www.amazon.co...s/dp/B00028N00M

[MrHappy]

Biol Psychiatry. 2005 Feb 15;57(4):343-50.

Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.
Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF.

Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA. carlezon@mclean.harvard.edu

BACKGROUND: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), we examined whether uridine would also produce antidepressant-like effects in rats. We also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. METHODS: We first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. We then combined sub-effective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. RESULTS: Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with OMG reduced immobility when given for 30 days, but not for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective dietary supplementation with OMG. CONCLUSIONS: Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.



Brain Res. 2007 Nov 28;1182:50-9. Epub 2007 Sep 21.

Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus.
Sakamoto T, Cansev M, Wurtman RJ.

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is an essential component of membrane phosphatides and has been implicated in cognitive functions. Low levels of circulating or brain DHA are associated with various neurocognitive disorders including Alzheimer's disease (AD), while laboratory animals, including animal models of AD, can exhibit improved cognitive ability with a diet enriched in DHA. Various cellular mechanisms have been proposed for DHA's behavioral effects, including increases in cellular membrane fluidity, promotion of neurite extension and inhibition of apoptosis. However, there is little direct evidence that DHA affects synaptic structure in living animals. Here we show that oral supplementation with DHA substantially increases the number of dendritic spines in adult gerbil hippocampus, particularly when animals are co-supplemented with a uridine source, uridine-5'-monophosphate (UMP), which increases brain levels of the rate-limiting phosphatide precursor CTP. The increase in dendritic spines (>30%) is accompanied by parallel increases in membrane phosphatides and in pre- and post-synaptic proteins within the hippocampus. Hence, oral DHA may promote neuronal membrane synthesis to increase the number of synapses, particularly when co-administered with UMP. Our findings provide a possible explanation for the effects of DHA on behavior and also suggest a strategy to treat cognitive disorders resulting from synapse loss.




Alzheimers Dement. 2008 Jan;4(1 Suppl 1):S153-68. Epub 2007 Dec 21.

Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses.
Cansev M, Wurtman RJ, Sakamoto T, Ulus IH.

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.

Although cognitive performance in humans and experimental animals can be improved by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing the quantities of particular neurotransmitters present within synaptic clefts or by acting directly on neurotransmitter receptors or signal-transduction molecules. We find that DHA also affects synaptic transmission in mammalian brain. Brain cells of gerbils or rats receiving this fatty acid manifest increased levels of phosphatides and of specific presynaptic or postsynaptic proteins. They also exhibit increased numbers of dendritic spines on postsynaptic neurons. These actions are markedly enhanced in animals that have also received the other two circulating precursors for phosphatidylcholine, uridine (which gives rise to brain uridine diphosphate and cytidine triphosphate) and choline (which gives rise to phosphocholine). The actions of DHA aere reproduced by eicosapentaenoic acid, another omega-3 compound, but not by omega-6 fatty acid arachidonic acid. Administration of circulating phosphatide precursors can also increase neurotransmitter release (acetylcholine, dopamine) and affect animal behavior. Conceivably, this treatment might have use in patients with the synaptic loss that characterizes Alzheimer's disease or other neurodegenerative diseases or occurs after stroke or brain injury.




Brain Res. 2007 Nov 28;1182:50-9. Epub 2007 Sep 21.

Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus.
Sakamoto T, Cansev M, Wurtman RJ.

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is an essential component of membrane phosphatides and has been implicated in cognitive functions. Low levels of circulating or brain DHA are associated with various neurocognitive disorders including Alzheimer's disease (AD), while laboratory animals, including animal models of AD, can exhibit improved cognitive ability with a diet enriched in DHA. Various cellular mechanisms have been proposed for DHA's behavioral effects, including increases in cellular membrane fluidity, promotion of neurite extension and inhibition of apoptosis. However, there is little direct evidence that DHA affects synaptic structure in living animals. Here we show that oral supplementation with DHA substantially increases the number of dendritic spines in adult gerbil hippocampus, particularly when animals are co-supplemented with a uridine source, uridine-5'-monophosphate (UMP), which increases brain levels of the rate-limiting phosphatide precursor CTP. The increase in dendritic spines (>30%) is accompanied by parallel increases in membrane phosphatides and in pre- and post-synaptic proteins within the hippocampus. Hence, oral DHA may promote neuronal membrane synthesis to increase the number of synapses, particularly when co-administered with UMP. Our findings provide a possible explanation for the effects of DHA on behavior and also suggest a strategy to treat cognitive disorders resulting from synapse loss.

[MrHappy]

http://www.patsnap.c...05112635A2.html

RESULTS [0072] In order to determine whether dopamine release is affected by uridine administration, animals provided UMP in their diets were assessed for dopamine production, both during and following neuron depolarization. Figures lA-E depict the release . profiles of a single uridine-fed rat and a single control rat over repeated stimulations. UMP administration enhanced release of DA (B) and 5-HT (E) both during and after depolarization. DOPAC (A), 5-HIAA ©, and HVA (D) exhibited lower basal levels in the UMP-fed animals, and release was increased, although by a smaller margin than DA and 5-HT, after but not during stimulation. UMP did not affect the total levels of DA and 5-HT in the striatum, while total striatal levels of DOPAC, 5-


http://web.mit.edu/n...imers-1126.html

MIT researchers have shown that a cocktail containing three compounds normally in the blood stream promotes growth of new brain connections and improves cognitive function in rodents. The treatment is now being tested in Alzheimer's patients and could hold promise for other brain diseases and injuries.
The mixture, which includes a type of omega-3 fatty acid, is part of a new approach to attacking Alzheimer's. That approach focuses on correcting the loss of synapses, or connections between neurons, which characterizes the disease.

http://www.patentgen...nt/4960759.html

3. Clinical tests

To evaluate whether the pharmacologic effects of uridine could result in a therapeutical confirmation, the compound was administered to a group of 40 psychotic subjects.

As it is well known in the medical practice that the neuroleptic drugs very often produce side effects of Parkinsonian type, such as rigidity, tremors and the like, and for this reason it is usual to associate anti Parkinson drugs to the anti psychotic drugs, the experimental pattern was organized so as to be able to evaluate whether uridine, thanks to its pharmacological properties, was able to be substituted in lieu of the anti Parkinson drug normally used.

Twenty psychotic subjects had been under treatment with neuroleptic drugs for various months and with anti Parkinsonian drugs because Parkinsonian symptoms had appeared among them. In our test, the anti Parkinsonian drug was substituted withuridine. Uridine was administered three times a day as 200 mg pills, along with haloperidol.

In twenty different psychotic subjects the treatment with anti Parkinsonian drug was interrupted for two weeks (wash out), before starting a treatment based on uridine and haloperidol, at the same dosages as the above indicated group.

Results

In the first group of subjects, uridine has shown itself able to efficaciously substitute the anti Parkinsonian drugs. In fact not one of the subjects has shown Parkinsonian symptoms in the two months period of treatment. In the absence of uridine, the tremor and rigidity symptoms usually appear within two to three weeks.

In the second group the tremor was already evident after the wash out period, before beginning the treatment with uridine.

With this treatment the Parkinsonian symptoms disappeared within the first ten days of treatment, and the symptoms did not reappear until two months after.

It can be concluded that uridine is a drug able to block the symptoms of Parkinson's disease when it is administered alone. Uridine is additionally able to inhibit the side effects of neuroleptic drugs, when it is administered together with thelatter in a treatment of psychotic subjects.

The pharmaceutically active agent according to the present invention can be provided for clinical use in pharmaceutical compositions for oral administration under the form of tablets, pills, granules, capsules, drops, syrups and the like togetherwith pharmaceutically acceptable excipients.

Moreover, the pharmaceutically active agent can be administered under the form of a pharmaceutical composition for parenteral administration, in the form of injectable solutes along with known pharmaceutically acceptable vehicles.

A preferred dosage for oral routes is 0.5-5 g/die referred to the pharmaceutically active agent.

[thedevinroy]

Awesome.

[MrHappy]

Seriously.

More people need to try this - I'm loving it. No stimulant effect, no ups and downs. You just have a clear head and things get easier.

It's like you are your normal happy self, just better and less impeded.

[Jq82]

http://www.ncbi.nlm....cles/PMC383240/

Was looking into Magnesium supplementation when I ran into the Uridine connection...thought it might be relevant.

[MrHappy]

Well, that is very useful! Thanks!

[wolfeye]

Effect of Oral CDP-Choline on Plasma Choline and
Uridine Levels in Humans

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.

http://web.mit.edu/d...www/pdf/972.pdf

[amark]

Covenant health sells Uridine capsules.made by Cardiovascular Research limited. I tried it but found that it had limited effect on bipolar depression. Please note that bipolar depression is not the same as other depressions and what is effective/ineffective for me may not be indicative of how anyone else might respond.

[rwac]

amark, Uridine is a nutrient not a drug, so you could just try to take more of it.

[MrHappy]

http://www.ncbi.nlm....ubmed/21945379/

Edited by MrHappy, 07 November 2012 - 11:55 PM.

[health_nutty]

I just bought some nutrional (brewers) yeast. The recommended dosage on the package is 3 tablespoons (20g). At 3% uridine, that would be 600mg of uridine. This is the low end of the recommended level.

[health_nutty]

Btw, I am also taking CDP-choline at 250mg a day. I wonder if the urdine from CDP-choline is more bioavailable.

[MrHappy]

I'm not a fan of ingesting that much yeast, being vego - yeast issues are common in vegetarians.

I get 25g uridine from here:
http://www.superiorn...tegory_Code=COG

And 100g alpha-gpc from here: (nootrabiolabs.com)
http://item.mobilewe...nid=00853200220

[rwac]

I just bought some nutrional (brewers) yeast. The recommended dosage on the package is 3 tablespoons (20g). At 3% uridine, that would be 600mg of uridine. This is the low end of the recommended level.

I had issues with brewers yeast, taking too much would trigger a tight chest, which i haven't had for years otherwise.

[health_nutty]

I just bought some nutrional (brewers) yeast. The recommended dosage on the package is 3 tablespoons (20g). At 3% uridine, that would be 600mg of uridine. This is the low end of the recommended level.

I had issues with brewers yeast, taking too much would trigger a tight chest, which i haven't had for years otherwise.

Weird, no issues here I feel amazing with it. Thanks for the heads up.

[thedevinroy]

I have tinea versicolor, so I ain't trying yeast anything. Too much bread or sugar gives me a skin reaction. There are a lot of studies out there on yeast that seem to conflicting for enhancing intelligence using yeast extracts. I've never took the time to really divulge, but I bet someone could find something negative if they put their mind into it.

Uridine is also found in sugar beats, broccoli, and organic meats? How is meat not organic... mutant meat or something? What?

Anyhow, broccoli extract is pretty popular. I just haven't tried it. Anybody have?

[FrankMH]

This looks like it should be something amazing. Those trial results speak for themselves, and it appears that some people have had some nice experiences. Can I just ask: How much more do we know about this combo since the last time it was brought to notable light on this Forum? It just sounds like this should have been getting Piracetam like coverage. I apologise if I sound retarded.

[MrHappy]

There appears to be a growing body of research on PubMed. The multiple patent applications for new delivery methods for uridine show that a few pharmaceutical companies can see commercial potential, but realise they can't patent uridine itself. <chuckle>

One of them has applied for a patent to use uridine as a Parkinson's disease modifer, though.

[health_nutty]

Uridine is also found in sugar beats, broccoli, and organic meats? How is meat not organic... mutant meat or something? What?

It should be "organ" meats.