2844 replies to this topic

[chrono]

Actually, I don't think it can be much more bioavailable than regular uridine under the tongue...I've been using 250-300mg uridine dissolved under the tongue twice a day for the last 9 days with impressive results

Sublingual administration is a good idea to bypass first-pass metabolism, but without comparing it to regular oral administration, it's not really possible to make comparisons about the bioavailability based on the subjective effects...

Triacetyluridine increases the regular oral bioavailability by about 7x. If you think sublingual administration is even better than this, that means you could be taking somewhere between 2-3g of uridine. I'd be cautious about this if I were you...

[MrHappy]

Yes, a lack of conflicting data is another consequence of 1 study in rats, and none in humans. A patent is not a study: it's written by someone who wants to sell you something, who is not required to tell you the truth if they can get away with not doing so. And the one you keep citing isn't even a good patent; it doesn't give us data, they just summarize their "findings" in a few sentences, with next to no details about the methodology. If anything, it is suggestive, but is not a reliable demonstration by any stretch.

OK, I agree that more information would go a long way.Tell you what, that patent cited 4 research papers and the 4 doctors involved in the patent. I'll see if I can locate them and if any of them still have the raw study data. I'm interested, anyway.

remember that L-DOPA has been the gold standard in masking the symptoms of PD for over 30 years

FTFY.

And again, there are many levels of probability between dismissal and 'absolutely proven.' This is somewhere in the middle.....It's a solidly preclinical hypothesis regarding one of the most difficult diseases to treat, and going from the studies here to efficacy in humans is a huge leap. I too hope it pans out.

Agreed.

I'm not sure why you think a theory about the pathogenesis of AD and PD is particularly important to this thread, as uridine doesn't seem to be involved with any of those mechanisms you mentioned, as far as I've read here...

It was offtopic, but related in the sense that Uridine is being trialed as a restorative treatment for AD.

there's still the issue of whether there are enough dopamine precursors to maintain the heightened release, and if the release will be in the appropriate parts of the brain.

The preclinical data looks solid, as does the patent background information in a number of the patents, as well as the one mentioned in more detail. There's only one way to find out for sure - more human studies in a controlled environment. I'm going to see if I can prod that along.

[chrono]

remember that L-DOPA has been the gold standard in masking the symptoms of PD for over 30 years

FTFY.

L-DOPA does more than mask the symptoms, including reducing mortality and potentially having an effect on the neurogenesis problem. We don't have perfect cures for any of the problems we discuss here, but feel free to dismiss L-DOPA completely if you think that's reasonable.

But all the comment was meant to convey was that, if there's an effective treatment for a disease, it doesn't require big pharma to get research done. Such research usually grows out of academic studies in the case of such unpatentable molecules.

Edited by chrono, 23 November 2011 - 04:56 AM.

[Hebbeh]

Actually, I don't think it can be much more bioavailable than regular uridine under the tongue...I've been using 250-300mg uridine dissolved under the tongue twice a day for the last 9 days with impressive results

Sublingual administration is a good idea to bypass first-pass metabolism, but without comparing it to regular oral administration, it's not really possible to make comparisons about the bioavailability based on the subjective effects...

Triacetyluridine increases the regular oral bioavailability by about 7x. If you think sublingual administration is even better than this, that means you could be taking somewhere between 2-3g of uridine. I'd be cautious about this if I were you...

I have to agree that is sound advice...and the double doses of the last couple days have felt like pushing the envelope with the tinnitus...but with the initial results so positive in respect to mental energy and clarity, I felt titrating further to ascertain the sweet spot prudent...and conclude, for me, 250mg sublingually twice daily provides the best subjective feeling of calm, clear, lucid mental energy and accompanying productivity. Hopefully, the carcinogenic aspect is overhyped. Regardless, most everything we are exposed too probably is a possible carcinogen...but as you have prudently pointed out...the poison is in the dose.

[MrHappy]

Hey, I think L-Dopa is great for treating the symptoms. It does cause a few side effects and has either tolerance issues or leads to dyskinesia.

I just also think it happens to be a profitable, monthly revenue for certain parties. Seems to be a recurring theme.

[MrHappy]

Actually, I don't think it can be much more bioavailable than regular uridine under the tongue...I've been using 250-300mg uridine dissolved under the tongue twice a day for the last 9 days with impressive results

Sublingual administration is a good idea to bypass first-pass metabolism, but without comparing it to regular oral administration, it's not really possible to make comparisons about the bioavailability based on the subjective effects...

Triacetyluridine increases the regular oral bioavailability by about 7x. If you think sublingual administration is even better than this, that means you could be taking somewhere between 2-3g of uridine. I'd be cautious about this if I were you...

I have to agree that is sound advice...and the double doses of the last couple days have felt like pushing the envelope with the tinnitus...but with the initial results so positive in respect to mental energy and clarity, I felt titrating further to ascertain the sweet spot prudent...and conclude, for me, 250mg sublingually twice daily provides the best subjective feeling of calm, clear, lucid mental energy and accompanying productivity. Hopefully, the carcinogenic aspect is overhyped. Regardless, most everything we are exposed too probably is a possible carcinogen...but as you have prudently pointed out...the poison is in the dose.

When I was testing Methylene Blue, I also had tinnitus issues. I read all sorts of things, some of which suggested that the tinnitus 'noise' observed is normal and your brain normally filters it out. Neural changes can require time for the 'filter' retrain. TRT seemed to help. Other text I read talked about calcium/magnesium imbalances and other nutrient problems. I was also taking a lot of minerals at the time, so could have been that, too..

Are you taking 250mg of TAU or is it UMP sublingually, BTW? Any co-factors..?

[Hebbeh]

Actually, I don't think it can be much more bioavailable than regular uridine under the tongue...I've been using 250-300mg uridine dissolved under the tongue twice a day for the last 9 days with impressive results

Sublingual administration is a good idea to bypass first-pass metabolism, but without comparing it to regular oral administration, it's not really possible to make comparisons about the bioavailability based on the subjective effects...

Triacetyluridine increases the regular oral bioavailability by about 7x. If you think sublingual administration is even better than this, that means you could be taking somewhere between 2-3g of uridine. I'd be cautious about this if I were you...

I have to agree that is sound advice...and the double doses of the last couple days have felt like pushing the envelope with the tinnitus...but with the initial results so positive in respect to mental energy and clarity, I felt titrating further to ascertain the sweet spot prudent...and conclude, for me, 250mg sublingually twice daily provides the best subjective feeling of calm, clear, lucid mental energy and accompanying productivity. Hopefully, the carcinogenic aspect is overhyped. Regardless, most everything we are exposed too probably is a possible carcinogen...but as you have prudently pointed out...the poison is in the dose.

When I was testing Methylene Blue, I also had tinnitus issues. I read all sorts of things, some of which suggested that the tinnitus 'noise' observed is normal and your brain normally filters it out. Neural changes can require time for the 'filter' retrain. TRT seemed to help. Other text I read talked about calcium/magnesium imbalances and other nutrient problems. I was also taking a lot of minerals at the time, so could have been that, too..

Are you taking 250mg of TAU or is it UMP sublingually, BTW? Any co-factors..?

UMP. My TAU hasn't arrived yet. I've been takng fish oil, lecithin, CDP-choline, ALC, and B complex for long time. Also take Ca, Mg, and Zn for a long time. And resveratrol sublingually for a long time.

[JChief]

@Hebbeh: What effects have you noticed from the CDP-Choline?

[Hebbeh]

Been using CDP choline for long time. Seems to give me a subtle mental energy boost but not very long lasting unlike the uridine. Tried CDP sublingually too and kicked in faster but nothing more than that. Uridine definitely seems WAY stronger.

[chrono]

Been using CDP choline for long time. Seems to give me a subtle mental energy boost but not very long lasting unlike the uridine. Tried CDP sublingually too and kicked in faster but nothing more than that. Uridine definitely seems WAY stronger.

Have you continued taking CDP choline during this uridine trial? And if so, how much?

[Hebbeh]

250mg CDP twice daily with the UMP

[chrono]

250mg CDP twice daily with the UMP

Wow...this is probably another reason why you're getting such effects, in addition to taking more free uridine than anyone else here several times over (if sublingual admin really does do something for bioavailability). It's cool that it's working so well, but I'll echo my earlier recommendation not to overdo things...

[Hebbeh]

Yeah, it's hard to say what blood and brain levels are. Effects are very clean, clear headed, lucid mental energy which I haven't felt for a long time....I'm 54 and suddenly I feel mentally 10+ years younger....just like I should...and want to feel. Also, I can't sleep for much more than 5-6 hours when I was just barely getting by on 7 before. Focus, productivity, and motivation are all much improved.

[Hebbeh]

Should add, my Dad, at 86, is in advanced stages of AD....and my short term memory has been declining with accompanying brain fog in recent years....so my motivation, in addition to improving memory and clear the fog is to try and avoid following my Dad's footsteps....and uridine has had the most positive effect to date of everything I've tried.

[MrHappy]

Truly awesome.

Some of the human trials were referring to 150mM of uridine in plasma. One of the other studies was experimenting with a range between .5g and 5g of uridine per day, all with positive results. I guess you've found your most efficient dose.

I am guessing you are intending to treat your father as well?

[spider]

OK.. UMP tastes mildly like salt, sublingually. I would attribute that to this particular product being uridine-5'-monophosphate disodium.

I'll see if I can make a subjective call about bioavailabilty over the next few hours, as opposed to regular dosing. For me, the short term benefits are more noticeable when I'm severely sleep-deprived.

OK, that's a little different. Seems to have a more focused and uplifting effect than normal. Cancelled out the drowsiness of bacopa, too.

Will have to try this again with some different/simpler parameters.

That's what I'm talking about! ;-)

Oke, so it looks like sublingual intake of UMP is superior to oral intake. But, is this also true for TAU?

[tintinet]

Noticing the tinnitus myself, especially if I'm reminded of it (like when reading this thread). Just started 250 mg CDP-choline and 300 mg uridine (P.0., not S.L., so far). I've been taking DHA/EPA and M.B. for some time. Also noticed improved balance. I practice martial arts, and find multiple kicks in several directions from a one legged stance more stable.

[MrHappy]

OK.. UMP tastes mildly like salt, sublingually. I would attribute that to this particular product being uridine-5'-monophosphate disodium.

I'll see if I can make a subjective call about bioavailabilty over the next few hours, as opposed to regular dosing. For me, the short term benefits are more noticeable when I'm severely sleep-deprived.

OK, that's a little different. Seems to have a more focused and uplifting effect than normal. Cancelled out the drowsiness of bacopa, too.

Will have to try this again with some different/simpler parameters.

That's what I'm talking about! ;-)

Oke, so it looks like sublingual intake of UMP is superior to oral intake. But, is this also true for TAU?

It seems to have a more pronounced short term effect. It was slightly irritating to my mouth, though. More testing needed to clarify if it still has similar sustained release characteristics, etc. You definitely get a lot more of a 'buzz' out of coffee and I'm not fond of stimulant-like effects in general. This appeared to give a mild 'high' effect, which is a bit different.

I haven't received my TAU yet, but I'll report on it once it arrives. If it's as water soluble as UMP, which vanishes near instantly in water, then I suspect it'll have a similar effect sublingually.

I wouldn't be suggesting everyone else tries this yet. There are a few questions I need to research. If you do, please report your experience.

[Hebbeh]

In general, I would agree with that assessment.

[MrHappy]

Seeing as some of the CDP-choline guys are taking up to 2g, per day, I'm (completely) guessing that there aren't any safety concerns with this type of dose. Anyone else have any thoughts on this?

[MrHappy]

Noticing the tinnitus myself, especially if I'm reminded of it (like when reading this thread). Just started 250 mg CDP-choline and 300 mg uridine (P.0., not S.L., so far). I've been taking DHA/EPA and M.B. for some time. Also noticed improved balance. I practice martial arts, and find multiple kicks in several directions from a one legged stance more stable.

I'd love to find the definitive research on tinnitus. It's quite an interesting topic to study, as it shows up many effects of neural changes and 'normal' reality filtering.

[GhostBuster]

I looked at some studies on TAU. In those studies they used amounts like + 5 GRAMS of TAU. That makes me wonder if 25 mg of TAU can be any good?

[JChief]

I looked at some studies on TAU. In those studies they used amounts like + 5 GRAMS of TAU. That makes me wonder if 25 mg of TAU can be any good?

Who knows but if those here are getting good results on just 250mg of UMP and we know that TAU is more bioavailable I am not too concerned. I am not trying to cure a mental illness I am just curious about mood enhancement/stability.

[spider]

I haven't received my TAU yet, but I'll report on it once it arrives. If it's as water soluble as UMP, which vanishes near instantly in water, then I suspect it'll have a similar effect sublingually.

I wouldn't be suggesting everyone else tries this yet. There are a few questions I need to research. If you do, please report your experience.

Thanks, MrHappy. I am following your uridine-topic with great interest. I am going to give uridine a try in 2 or 3 months or so because first I am starting with new stack next week.

I looked at some studies on TAU. In those studies they used amounts like + 5 GRAMS of TAU. That makes me wonder if 25 mg of TAU can be any good?

GhostBuster,
Yeah, 5 grams of TAU sounds like a whopping dosage to me too. According to Chrono, the bioavailability of TAU is 5 to 7 times higher than regular uridine. So this would equivalent to 25- 35 grams of UMP. :o

[MrHappy]

After 2 days at the sublingual dose of 250mg, the biggest difference I've noticed is focus. It's similar to the focus levels I saw on 1mg of MB. Well over 15 hours and that hasn't faded. The trade-off seems to be less emotional response.

Not sure if I would perhaps save this effect for crazy work/study requirements. It's very useful, I just like my emotions. Subjectively, it feels like perhaps oxytocin levels have been modulated - similar to a week of abstinence.

[MrHappy]

Uridine patented and licensed for treating bipolar disorder:
http://www.news-medi...3/31/47687.aspx

[JChief]

Uridine patented and licensed for treating bipolar disorder:
http://www.news-medi...3/31/47687.aspx

“While we are disappointed with the top-line results of the study, we plan to conduct further evaluation of the data including the observation of differences between the patients treated in academic and commercial sites to determine if there is a path forward with RG2417,” stated Walter C. Herlihy, President and Chief Executive Officer of Repligen Corporation. “In the short term, our efforts remain focused on completing the Phase 3 trial for RG1068, our pancreatic imaging agent, for which we expect to announce results later this month, as well as advancing our lead compounds for Friedreich’s ataxia and for spinal muscular atrophy into the clinic while maintaining a low cash burn and a strong balance sheet. For FY2011, ending March 31, 2011, we anticipate $27-$28M in revenues, and $60M in cash and investments and no debt.”

http://www.businessw...-RG2417-Bipolar
Mar 7, 2011

[MrHappy]

Why were the academic results different to the stage 2 trials, I wonder?

[MrHappy]

More research:

Dopamine's role in neurogenesis:
http://www.cell.com/...t/S1934-5909(11)00052-X?switch=standard

Uridine modulates stimulant induced dopamine release:
http://ebm.rsmjourna...4/1/49.abstract
And neuroleptics:
http://www.ncbi.nlm....ubmed/20504471/

Yet increases potassium-evoked dopamine release:
http://www.ncbi.nlm....ubmed/16055952/

Here is another patent, this time by Dr Wurtman, author of a number of the research papers on page 1 and related to the Fortasyn Connect/Souvenaid product, for uridine as a treatment for Parkinsons:
http://www.wipo.int/...=PCTDescription

Wurtman, et al., on restorative properties of uridine+DHA in rat model of parkinsons:
http://wurtmanlab.mi...ic/pdf/1034.pdf

UMP + Choline improves spatial awareness and selective attention in spontaneously hypertensive rats:
http://www.sciencedi...074742703000248

Hey! I found the original patent document for that antipsychotic/antiparkinsonian uridine trial from 1989. It makes a lot more sense when it hasn't been garbled:
http://docs.docstoc....a223d245da5.pdf

Case studies on developmental disorders and treatment with uridine:
http://m.pnas.org/co...4/21/11601.full

[bacopa]

guys I'm trying uridine from the company Mr. Kitty, one of them, showed me, along with high DHA, and choline, and lions mane, and some others.

My problem is a feel like I have no brain left. Seriously, like there is air there, and not a feeling I used to have like a basic conscious feeling.

I'm thinking this could be from anoxia damage that we don't know exactly the degree, nor obviously how these things play out, as every brain injury is different, and of course in my other thread I mentioned antipsychotics decreasing brain volume by at least 1% each year in several studies. I am sorry I do not have the energy, nor memory at this second to show the study, but there is a famous one on Macabee monkeys that showed 2nd generation atypical antipsychotics, the one's they give to everyone these days, ate away at brain tissue by 15% each year, I attended a lecture with Robert Whitaker, in Mass, who wrote "Anatomy of an Epidemic," on big pharmas, lies about what they are destroying people with...

Then there's electroshock, I spent the last year interviewing, amnesic people who couldn't do basic math, nor remember years, decades of life memories, some forgot how to drive, and so much literature on this, I"d be happy to post, if anyone's interested.

Finally that brings me to my present day problems, of having multiple insults to my brain, so some consider ECT to be "closed head injury," while even pro ECT docs came out in a study in 07 proving shocking the brain at 450 volts .9 ampiers of currrent, proved permanent brain damage in 100% of people out of 357, here is the write up of the study, http://www.huffingto...ie_b_44734.html, anyway in short, the voltage and I believe current is actually higher today than in the form that Ernest Hemingway got, in the 50's and he committed suicide as a result, with his famous quote that ECt destroyed his abiltiy to write, can be found on his wikipedia page.

Anyway. My brain is so damaged, that like any other person, I am desperate, to find a way to grow neurons back...From all that I have read about ECT, neurogenisis, is especially difficult do to how high current uniquely destroys brain tissue, again, I can show all of this or it can be found online, once you get past the ECT and pharma + hospital tie in and backed studies. (This is the type of thing I used to be able to explain much better.

So I'm keeping on top of this thread, and if anyone knows of things that can increase neurogenesis, and neuroprotect, besides all that has been discussed please tell me, I'm looking into PQQ.

Last question, how much uridine orally should one attempt? I know there are better ways to make uridine bioavailable, but I don't have the stamina right now to research this.