![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by Peter S. on April 9, 2005, at 0:33:27
There has been a big buzz lately about 1 study that found uridine combined with Omega 3s effective for depression:
http://cms.psychologytoday.com/articles/pto-20050325-000002.htmlThe study even showed that uridine by itself caused an immediate anti-depressant effect! I want to know where I can get some of this stuff or how many sugar beets or other foods I have to eat. It sounds like there have been no other studies so I guess the results need to be taken with a grain of salt. I've tried fish oil for long periods but have never noticed any mood enhancement.
Any feedback or ideas?
Peter
Posted by Larry Hoover on April 10, 2005, at 8:28:56
In reply to Uridine- Where do I get it?, posted by Peter S. on April 9, 2005, at 0:33:27
> There has been a big buzz lately about 1 study that found uridine combined with Omega 3s effective for depression:
> http://cms.psychologytoday.com/articles/pto-20050325-000002.html
>
> The study even showed that uridine by itself caused an immediate anti-depressant effect! I want to know where I can get some of this stuff or how many sugar beets or other foods I have to eat. It sounds like there have been no other studies so I guess the results need to be taken with a grain of salt. I've tried fish oil for long periods but have never noticed any mood enhancement.
>
> Any feedback or ideas?
>
> PeterUridine is one component of RNA. I don't have a clue how effective they might be, but I have seen RNA supplements. You'd be getting a fraction of that mixture in the form of uridine.
Given my experience watching the supplement industry, you can expect uridine supplements to hit the shelves within a couple of months.
I could get uridine from a chemical supply house, for example. It's pretty expensive. And, with the new demand for it that might soon exist, you can bet it's going to take a while for the supply to increase to match the demand.
Expect high prices, and poor availability, especially if the darn stuff works.
Lar
Posted by joebob on April 10, 2005, at 11:18:19
In reply to Re: Uridine- Where do I get it? » Peter S., posted by Larry Hoover on April 10, 2005, at 8:28:56
much??
any ideas??
Posted by Larry Hoover on April 10, 2005, at 11:54:20
In reply to the article mentions uridine is in molasses..how, posted by joebob on April 10, 2005, at 11:18:19
> much??
> any ideas??Too much sugar in there, relative to molasses. Can't hurt to use molasses instead of another sweetener (used rationally), but you can't use molasses as a uridine supplement, per se.
Lar
Posted by joebob on April 10, 2005, at 13:08:14
In reply to Re: the article mentions uridine is in molasses..how » joebob, posted by Larry Hoover on April 10, 2005, at 11:54:20
Posted by Peter S. on April 10, 2005, at 22:13:03
In reply to Re: Uridine- Where do I get it? » Peter S., posted by Larry Hoover on April 10, 2005, at 8:28:56
Thanks Larry,
When I hear about this kind of thing my mind takes huge ridiculous leaps like "maybe this is the natural stuff that will be 'the answer' and make Prozac et al obsolete!" The pharmaceutical indudstry sure wouldn't like that. Of course then I wake up...
> > There has been a big buzz lately about 1 study that found uridine combined with Omega 3s effective for depression:
> > http://cms.psychologytoday.com/articles/pto-20050325-000002.html
> >
> > The study even showed that uridine by itself caused an immediate anti-depressant effect! I want to know where I can get some of this stuff or how many sugar beets or other foods I have to eat. It sounds like there have been no other studies so I guess the results need to be taken with a grain of salt. I've tried fish oil for long periods but have never noticed any mood enhancement.
> >
> > Any feedback or ideas?
> >
> > Peter
>
> Uridine is one component of RNA. I don't have a clue how effective they might be, but I have seen RNA supplements. You'd be getting a fraction of that mixture in the form of uridine.
>
> Given my experience watching the supplement industry, you can expect uridine supplements to hit the shelves within a couple of months.
>
> I could get uridine from a chemical supply house, for example. It's pretty expensive. And, with the new demand for it that might soon exist, you can bet it's going to take a while for the supply to increase to match the demand.
>
> Expect high prices, and poor availability, especially if the darn stuff works.
>
> Lar
>
>
Posted by JLxx on May 4, 2005, at 12:13:54
In reply to Re: Uridine- Where do I get it? » Larry Hoover, posted by Peter S. on April 10, 2005, at 22:13:03
I went in search of more info about uridine and found out a few interesting things and also have some questions.
It's of interest in counteracting toxicity in cancer treatments and also AIDS:
http://annonc.oupjournals.org/cgi/content/abstract/4/4/317
http://www.aidsmeds.com/Fusetalk/messageview.cfm?catid=10&threadid=15506&FTVAR_MSGDBTABLE=
http://www.powerhealthreview.com/show.php?id=14
The link from the AIDS forum has info about a product called NucleomaxX. http://www.nucleomaxx.com/ which apparently does increase uridine: http://www.aegis.com/conferences/6thLipo/30.html
The science here is incomprehensible to me, but do I gather that there is some connection to magnesium and uridine? More or "enough" magnesium means more or enough uridine? http://www.pnas.org/cgi/content/abstract/102/3/662
I wondered if there was some kind of precursor to uridine and am not sure of the science here either, but these articles discuss citicolene:
"Citicoline, a dietary supplement ingredient, is a precursor of phosphatidylcholine, a type of phospholipid that is a component of cell membranes. When the body absorbs Citicoline, it is broken down into uridine and choline. Citicoline reforms in the brain and is used as rawmaterial for phosphatidylcholine synthesis. It is believed that Citicoline stabilizes the membranes of neuronal cells through the metabolic pathway. and inhibits the formation of free fatty acids, substances exhibitingcytotoxicity. Citicoline is also converted to acetylcholine, a neurotransmitter.Research indicates Citicoline has a targeted action for increasing brainphospholipid synthesis. Citicoline is absorbed as a form of its hydrolyzedproducts, uridine and choline. Within the brain, neuronal cells convert uridine into cytidine, which reacts with choline to produce Citicoline.Citicoline then moves into the metabolic pathway of phosphatidylcholineproduction in the brain."
Citicholine is CDP choline:
"CDP choline is metabolized to yield the free nucleotide cytidine and choline. Scientific research demonstrates that CDP Choline consumption promotes brain metabolism by enhancing the synthesis of acetylcholine, restoring phospholipid content in the brain and regulation of neuronal membrane excitability and osmolarity (by its effect on the ATP-dependent sodium and potassium pumps)." http://www.raysahelian.com/cdp.html
Another article discussing choline and the research by Richard Wurtman and others,
http://www.sciencenews.org/articles/20031122/food.aspOn the bottom of this page about Wurtman he says,
http://web.mit.edu/bcs/people/wurtman.shtml"Over the years we have found that the rates at which brain cells produce a number of important compounds, for example the neurotransmitters serotonin, dopamine, and acetylcholine - normally depend on brain concentrations of their precursors (tryptophan, tyrosine, and choline). It now appears that the syntheses of phosphatidylcholine [PC] and the other major membrane phospholipids also depend on precursor availability. The main circulating precursor is cytidine (or, in humans, uridine), a compound that is not present in the final phospholipid product, but which, when phosphorylated to CTP, controls a key step in phosphatide synthesis (i.e., the combining of phosphocholine and CTP to form endogenous cytidyldiphosphocholine [CDP-choline]). When cultured neurons are stimulated to produce neurites, for example by exposing them to Nerve Growth Factor, another precursor- diacylglycerol-can also become limiting in phosphatide synthesis.
These observations have led to a new strategy for developing drugs to treat strokes and brain injury, i.e., diminish the ultimate size of the damaged area (which usually expands during the initial week after the stroke, because of the release of toxic compounds, like arachidonic acid oxidation products from nearly dying cells), and facilitate the regrowth of damaged axons and synapses by surviving neurons, by promoting the synthesis of PC (which sopps up free arachidonic acid). Both effects can be obtained experimentally, by giving a drug, Citicoline, that breaks down to blood choline and cytidine (uridine in humans), or by giving a constituent of infant formulas, UMP, that raises blood uridine levels. The blood changes increase CTP and phosphocholine levels in the brain, promoting the incorporation of excess free arachidonic acid into PC and thus increasing neuronal membranes."
Note those last few sentences. Raising blood uridine levels by using infant formula?
Sure enough, check out the UMP in these formulas:
http://www.abbott.com.sg/family/popups/popup-similac.htm
http://www.brightbeginnings.com/professionals/pro_nucleotides.asp
And this article
http://www.fortwayne.com/mld/newssentinel/living/10989579.htm on helping depressed kids without drugs, also mentions baby food"Though the natural substance uridine is still hard to come by_it's found in breast milk and enriched baby food_Harvard researchers have found that when uridine is combined with omega-3 fatty acids, it can prevent signs of depression just as well as antidepressants."
I didn't really look for UMP in baby food, but it didn't come right up in a Google search suggesting it's not that common.
I'm left with a few questions: Does taking CDP-choline equal taking uridine? What kinds of depressive variations might it be contraindicated for?
Uridine is listed directly on this wholesale supplier's site, so why does it have to be made into a drug? http://www.aminoactives.com/available.cfm
If it can be synthetized into baby formula, again why are their "drug" trials about it?
Would it be worth a try to guzzle baby formula combined with fish oil to try to duplicate the test results?? Sounds harmless enough at least. :) How much would it take? Or would CDP-choline be a better trial? Or have I misunderstood much of this?
JL
> Thanks Larry,
>
> When I hear about this kind of thing my mind takes huge ridiculous leaps like "maybe this is the natural stuff that will be 'the answer' and make Prozac et al obsolete!" The pharmaceutical indudstry sure wouldn't like that. Of course then I wake up...
>
>
>
> > > There has been a big buzz lately about 1 study that found uridine combined with Omega 3s effective for depression:
> > > http://cms.psychologytoday.com/articles/pto-20050325-000002.html
> > >
> > > The study even showed that uridine by itself caused an immediate anti-depressant effect! I want to know where I can get some of this stuff or how many sugar beets or other foods I have to eat. It sounds like there have been no other studies so I guess the results need to be taken with a grain of salt. I've tried fish oil for long periods but have never noticed any mood enhancement.
> > >
> > > Any feedback or ideas?
> > >
> > > Peter
> >
> > Uridine is one component of RNA. I don't have a clue how effective they might be, but I have seen RNA supplements. You'd be getting a fraction of that mixture in the form of uridine.
> >
> > Given my experience watching the supplement industry, you can expect uridine supplements to hit the shelves within a couple of months.
> >
> > I could get uridine from a chemical supply house, for example. It's pretty expensive. And, with the new demand for it that might soon exist, you can bet it's going to take a while for the supply to increase to match the demand.
> >
> > Expect high prices, and poor availability, especially if the darn stuff works.
> >
> > Lar
> >
> >
>
>
Posted by itsme2003 on May 6, 2005, at 1:14:56
In reply to Re: Where to find, questions....Larry, » Peter S., posted by JLxx on May 4, 2005, at 12:13:54
I did some research to find a source for a supplement and it is available, but it is very expensive.
As JLxx said, it is of interest to the AIDS community.
At http://www.powerhealthreview.com/show.php?id=14 is an interview about Dr. Ulrich A. Walker on Uridine and Mitochondrial Toxicity. He says in part:
"Uridine can be bought at the chemist but the costs there are prohibitive to be used long-term by anybody. NucleomaxX is a dietary supplement that comes in sachets to be dissolved in water, milk or juice. It contains Mitocnol, a sugar cane extract with high amounts (18%) of nucleosides." He doesn't say what percentage of these nucleosides are uridine, but since sugar cane is listed as one of the best sources for uridine, then it's probably reasonably high.
Later he gives the NucleomaxX website as www.nucleomaxX.com.
The NucleomaxX website doesn't sell the product itself, instead referring to http://www.tabsandmore.com in general and specifically http://www.tabsandmore.com/wstore/contentServlet/pid1000086.htm?parent=1001230 for NucleomaxX. It's EUR 87.75 for nine-packets (which would be a one-month's supply for an AIDS patient) so it's very pricey. AIDS patients take 3 packets per day on 3 consecutive days once per month. It's possible the dosing would be completely different for depression, so this amount might last longer than one month when used to treat depression. My guess would be that depression would require (two or three times) daily dosing with much smaller amounts.
I think it's likely that once more demand exists for uridine supplements then the prices will come down to more reasonable levels, although it will probably remain as one of the more expensive supplements.
Posted by itsme2003 on May 7, 2005, at 23:58:07
In reply to Re: Where to find, questions....Larry,, posted by itsme2003 on May 6, 2005, at 1:14:56
You can also buy it here as a lab chemical:
http://www.sciencelab.com/page/S/PVAR/10428/SLU1147It is a bit on the expensive side, although I guess it depends on how much you need to take.
25 g $57.71
100 g $201.83
1 kg $573.89
Posted by Larry Hoover on May 21, 2005, at 14:52:33
In reply to Re: Where to find, questions....Larry, » Peter S., posted by JLxx on May 4, 2005, at 12:13:54
I really like the work you do. It is very thorough and progressive in scope.
> I went in search of more info about uridine and found out a few interesting things and also have some questions.
>
> It's of interest in counteracting toxicity in cancer treatments and also AIDS:
>
> http://annonc.oupjournals.org/cgi/content/abstract/4/4/317Not relevant to people not taking the chemotherapy drug.
> http://www.aidsmeds.com/Fusetalk/messageview.cfm?catid=10&threadid=15506&FTVAR_MSGDBTABLE=
>
> http://www.powerhealthreview.com/show.php?id=14Not relevant to people not taking AIDS drugs.
> The link from the AIDS forum has info about a product called NucleomaxX. http://www.nucleomaxx.com/ which apparently does increase uridine: http://www.aegis.com/conferences/6thLipo/30.htmlExpensive! Hoi!
> The science here is incomprehensible to me, but do I gather that there is some connection to magnesium and uridine? More or "enough" magnesium means more or enough uridine? http://www.pnas.org/cgi/content/abstract/102/3/662
Unless you're grossly deficient in magnesium, and those other uptake factors, this is not an issue. The experiment was to determine if one or more than one uptake mechanisms existed, and they found the answer: more than one.
> I wondered if there was some kind of precursor to uridine and am not sure of the science here either, but these articles discuss citicolene:> Another article discussing choline and the research by Richard Wurtman and others,
> http://www.sciencenews.org/articles/20031122/food.asp
>
> On the bottom of this page about Wurtman he says,
> http://web.mit.edu/bcs/people/wurtman.shtml> I'm left with a few questions: Does taking CDP-choline equal taking uridine?
This question was answered with two simple keywords in Pubmed: Wurtman uridine
Sometimes, it's that simple.
Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
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. dick@mit.edu
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.
> What kinds of depressive variations might it be contraindicated for?
This question, I cannot answer.
> Uridine is listed directly on this wholesale supplier's site, so why does it have to be made into a drug? http://www.aminoactives.com/available.cfm
>
> If it can be synthetized into baby formula, again why are their "drug" trials about it?Obtaining it in pure chemical form is the tricky part. Obtaining it as a component of a mixture, or in semi-pure form, is not nearly so difficult (or costly). If you buy from a chemical house, you're paying for isolating the chemical.
The "drug trials" were to counteract the specific side-effects of drugs. For example, the HIV virus is an RNA-dependent organism. Uridine is a constituent of RNA. Some anti-HIV drugs disturb all RNA metabolism, including that of the host (the human). We need RNA, too. So, interventions that boosted uridine were being tried, to reduce side-effects.
> Would it be worth a try to guzzle baby formula combined with fish oil to try to duplicate the test results?? Sounds harmless enough at least. :) How much would it take? Or would CDP-choline be a better trial? Or have I misunderstood much of this?
>
> JLCDP-choline shows evidence of substantially boosting blood uridine levels. I don't think there's enough in baby formula to make a big difference, unless you tried to subsist on it.
Here's something I came across while investigating the biochemistry of uridine.
Orotic acid.
We've heard of that, lots of times. Lithium orotate is the salt of lithium cations and oratic acid anions.
Another name for orotic acid is uracil-6-carboxylic acid.
Uracil is one ribose sugar away from uridine.
So, maybe all those people thinking they were treating themselves with lithium were feeling better from the orotic acid?
I'm speculating, on that.
However, magnesium orotate is quite inexpensive, here:
http://vitanetonline.com/description/71060-K/vitamins/Magnesium-Orotate/Other sources are four times that cost, and I don't know why.
Lar
Posted by JLx on May 24, 2005, at 23:11:45
In reply to Re: Where to find, questions....Larry, » JLxx, posted by Larry Hoover on May 21, 2005, at 14:52:33
> I really like the work you do. It is very thorough and progressive in scope.
Thank you very much!
> > I went in search of more info about uridine and found out a few interesting things and also have some questions.
> >
> > It's of interest in counteracting toxicity in cancer treatments and also AIDS:
> >
> > http://annonc.oupjournals.org/cgi/content/abstract/4/4/317
>
> Not relevant to people not taking the chemotherapy drug.
>
> > http://www.aidsmeds.com/Fusetalk/messageview.cfm?catid=10&threadid=15506&FTVAR_MSGDBTABLE=
> >
> > http://www.powerhealthreview.com/show.php?id=14
>
> Not relevant to people not taking AIDS drugs.
>
> > The link from the AIDS forum has info about a product called NucleomaxX. http://www.nucleomaxx.com/ which apparently does increase uridine: http://www.aegis.com/conferences/6thLipo/30.html
>
> Expensive! Hoi!
>
> > The science here is incomprehensible to me, but do I gather that there is some connection to magnesium and uridine? More or "enough" magnesium means more or enough uridine? http://www.pnas.org/cgi/content/abstract/102/3/662
>
> Unless you're grossly deficient in magnesium, and those other uptake factors, this is not an issue. The experiment was to determine if one or more than one uptake mechanisms existed, and they found the answer: more than one.
>
> > I wondered if there was some kind of precursor to uridine and am not sure of the science here either, but these articles discuss citicolene:
>
> > Another article discussing choline and the research by Richard Wurtman and others,
> > http://www.sciencenews.org/articles/20031122/food.asp
> >
> > On the bottom of this page about Wurtman he says,
> > http://web.mit.edu/bcs/people/wurtman.shtml
>
> > I'm left with a few questions: Does taking CDP-choline equal taking uridine?
>
> This question was answered with two simple keywords in Pubmed: Wurtman uridine
>
> Sometimes, it's that simple.
>
> Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
> 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. dick@mit.edu
>
> 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.So, it sounds like 500 mg to 1000 mg citicholine taking along with fish oil might be worth a shot at duplicating those test results mentioned in Peter's original post: http://cms.psychologytoday.com/articles/pto-20050325-000002.html
> > What kinds of depressive variations might it be contraindicated for?
>
> This question, I cannot answer.
>
> > Uridine is listed directly on this wholesale supplier's site, so why does it have to be made into a drug? http://www.aminoactives.com/available.cfm
> >
> > If it can be synthetized into baby formula, again why are their "drug" trials about it?
>
> Obtaining it in pure chemical form is the tricky part. Obtaining it as a component of a mixture, or in semi-pure form, is not nearly so difficult (or costly). If you buy from a chemical house, you're paying for isolating the chemical.
>
> The "drug trials" were to counteract the specific side-effects of drugs. For example, the HIV virus is an RNA-dependent organism. Uridine is a constituent of RNA. Some anti-HIV drugs disturb all RNA metabolism, including that of the host (the human). We need RNA, too. So, interventions that boosted uridine were being tried, to reduce side-effects.Sorry, I didn't realize I was referring to Peter's post in another thread. http://www.dr-bob.org/babble/20050408/msgs/483146.html
> > Would it be worth a try to guzzle baby formula combined with fish oil to try to duplicate the test results?? Sounds harmless enough at least. :) How much would it take? Or would CDP-choline be a better trial? Or have I misunderstood much of this?
> >
> > JL
>
> CDP-choline shows evidence of substantially boosting blood uridine levels. I don't think there's enough in baby formula to make a big difference, unless you tried to subsist on it.
>
> Here's something I came across while investigating the biochemistry of uridine.
>
> Orotic acid.
>
> We've heard of that, lots of times. Lithium orotate is the salt of lithium cations and oratic acid anions.
>
> Another name for orotic acid is uracil-6-carboxylic acid.
>
> Uracil is one ribose sugar away from uridine.
>
> So, maybe all those people thinking they were treating themselves with lithium were feeling better from the orotic acid?
>
> I'm speculating, on that.
>
> However, magnesium orotate is quite inexpensive, here:
> http://vitanetonline.com/description/71060-K/vitamins/Magnesium-Orotate/
>
> Other sources are four times that cost, and I don't know why.
>
> LarVery intriguing! I love magnesium, as you know, so I am definitely going to give that form a try.
JL
Posted by Larry Hoover on May 25, 2005, at 8:10:14
In reply to Re: Uridine, CDP choline, magnesium orotate » Larry Hoover, posted by JLx on May 24, 2005, at 23:11:45
> So, it sounds like 500 mg to 1000 mg citicholine taking along with fish oil might be worth a shot at duplicating those test results mentioned in Peter's original post: http://cms.psychologytoday.com/articles/pto-20050325-000002.html
Sounds like.
> Sorry, I didn't realize I was referring to Peter's post in another thread. http://www.dr-bob.org/babble/20050408/msgs/483146.html
I didn't see that post. They're using triacetyuridine as a prodrug (converts to uridine). Of course, they're using a patented form. Exclusive use, high price.
> > However, magnesium orotate is quite inexpensive, here:
> > http://vitanetonline.com/description/71060-K/vitamins/Magnesium-Orotate/
> >
> > Other sources are four times that cost, and I don't know why.
> >
> > Lar
>
> Very intriguing! I love magnesium, as you know, so I am definitely going to give that form a try.
>
> JLWell, it might be discontinued, so hurry to get some.
Lar
Posted by Larry Hoover on May 25, 2005, at 8:36:11
In reply to Re: Uridine, CDP choline, magnesium orotate » Larry Hoover, posted by JLx on May 24, 2005, at 23:11:45
> So, it sounds like 500 mg to 1000 mg citicholine taking along with fish oil might be worth a shot at duplicating those test results mentioned in Peter's original post: http://cms.psychologytoday.com/articles/pto-20050325-000002.html
I'm not usually one for combinations (I can combine things on my own), but look what's in this one:
http://store.yahoo.com/iherb/neuro.htmlIt contains more citicholine than the straight caps (250 mg dose), and a whole lot of other good stuff, for only a few bucks more.
http://store.yahoo.com/iherb/cholin2.html
Lar
Posted by Larry Hoover on May 25, 2005, at 22:19:03
In reply to Re: Uridine, CDP choline, magnesium orotate » Larry Hoover, posted by JLx on May 24, 2005, at 23:11:45
P.S. I just ordered some citicoline (I know that's spelled wrong, but that's how they spell it on the label). It sounds to good an opportunity to pass up.
I ordered some mag orotate, too.
Oh, and some SAMe. I don't believe I ever tried it. Can't remember, one way or the other. But it's $9.00 a pack at iherb. Natrol brand. I dunno if it's good stuff or not, but it's cheap.
Lar
Posted by JLx on May 26, 2005, at 12:43:02
In reply to Re: Where to find, questions....Larry, » JLxx, posted by Larry Hoover on May 21, 2005, at 14:52:33
> CDP-choline shows evidence of substantially boosting blood uridine levels. I don't think there's enough in baby formula to make a big difference, unless you tried to subsist on it.
>
> Here's something I came across while investigating the biochemistry of uridine.
>
> Orotic acid.
>
> We've heard of that, lots of times. Lithium orotate is the salt of lithium cations and oratic acid anions.
>
> Another name for orotic acid is uracil-6-carboxylic acid.
>
> Uracil is one ribose sugar away from uridine.
>
> So, maybe all those people thinking they were treating themselves with lithium were feeling better from the orotic acid?
>
> I'm speculating, on that.
>
> However, magnesium orotate is quite inexpensive, here:
> http://vitanetonline.com/description/71060-K/vitamins/Magnesium-Orotate/
>
> Other sources are four times that cost, and I don't know why.
>
> LarI wonder if the cost is related to the amount of elemental magnesium. The KAL brand doesn't say, but some others I've seen do and it's low. Examples:
400mg equiv. to elemental magnesium 26.2mg.
39.4 mg Magnesium (100% as fully reacted CertiPure Magnesium Orotate, 500mg)
Magnesium orotate 770 mg *
Magnesium (elemental).. 50 mg 18%
Orotic Acid .. 720 mg *Beyond a Century sells magnesium orotate in powder form. 1/4 tsp equals 73 mg elemental magnesium, and there are 200 of those in their container; you'd need 1 and 3/4 tsp daily to get 511 mg of magnesium. At their price of $22.50, that's 90 cents per day.
If the KAL brand you linked to has the same amount of elemental magnesium per unit, then 200 mg is 14 mg of magnesium. To get approx 500 mg/day you'd need 35 capsules a day, at $6.83 for 60 count, that's approx 11 cents per unit, or $3.85/day.
I'm going to order from BAC. I'm sure it will taste terrible though.Speaking of orotic acid....
At the bottom of this page about lithium orotate there's some discussion of orotic acid and specifically magnesium orotate, including that "the body preferentially uses magnesium orotate for promoting uridine synthesis".
"The enzyme orotate phosphoribosyltransferase (OPRTase), which is found in organisms ranging from yeast to humans, is responsible for catalyzing the first step in the conversion of orotic acid into uridine. It does so by facilitating the attachment of a ribose plus phosphate group to OA. The net result is the formation of a molecule named OMP (orotidine 5'-monophosphate), which in turn is the immediate precursor to UMP (uridine 5'-monophosphate).
Because the enzyme OPRTase requires magnesium ions for its activity, some researchers wondered whether a magnesium complex of orotic acid might be involved in binding orotate to the enzyme.10 They found that the true substrate for OPRTase is not orotate itself but rather a magnesium orotate complex. The fact that the complex is electrically neutral compared to the negatively charged orotate ion means that the complex is more easily transportable to the active site of the enzyme.10 These researchers suggested that the magnesium complex helps position orotate within the enzyme in the proper orientation for conversion to OMP. In the process the magnesium ion in the complex gets exchanged with the magnesium ion bound to the active site of the enzyme, the net result being that one magnesium ion is released.
So far, so good. Following up on Nieper's hint, we see that orotate-and specifically magnesium orotate-can interact with the pentose phosphate pathway (PPP) to generate OMP and ultimately uridine."
http://www.lithiumorotate.com/howitworks.html
So, it sure sounds like between CDP-choline and magnesium orotate it should be possible to significantly increase uridine.
From the earlier link about Richard Wurtman, http://web.mit.edu/bcs/people/wurtman.shtml, he says:
"It now appears that the syntheses of phosphatidylcholine [PC] and the other major membrane phospholipids also depend on precursor availability. The main circulating precursor is cytidine (or, in humans, uridine), a compound that is not present in the final phospholipid product, but which, when phosphorylated to CTP, controls a key step in phosphatide synthesis (i.e., the combining of phosphocholine and CTP to form endogenous cytidyldiphosphocholine [CDP-choline])."
So uridine increases phosphatidylcholine?
In his next paragraph he mentions arachidonic acid,
"These observations have led to a new strategy for developing drugs to treat strokes and brain injury, i.e., diminish the ultimate size of the damaged area (which usually expands during the initial week after the stroke, because of the release of toxic compounds, like arachidonic acid oxidation products from nearly dying cells), and facilitate the regrowth of damaged axons and synapses by surviving neurons, by promoting the synthesis of PC (which sopps up free arachidonic acid). Both effects can be obtained experimentally, by giving a drug, Citicoline, that breaks down to blood choline and cytidine (uridine in humans), or by giving a constituent of infant formulas, UMP, that raises blood uridine levels. The blood changes increase CTP and phosphocholine levels in the brain, promoting the incorporation of excess free arachidonic acid into PC and thus increasing neuronal membranes."
So, increasing uridine and therefore PC also decreases arachidonic acid?
Interesting in terms of depression in view of this recent study done on rats:
Discussion: http://www.medicalnewstoday.com/medicalnews.php?newsid=25134
Study: http://www.jlr.org/cgi/content/abstract/C500003-JLR200v1
"They examined the brains of the depressed rats and compared them with brains from normal rats. Surprisingly, they found that the main difference between the two types of rats was in omega-6 fatty acid levels and not omega-3 fatty acid levels. Specifically, they discovered that brains from rats with depression had higher concentrations of arachidonic acid, a long-chain unsaturated metabolite of omega-6 fatty acid. ...
"The finding that in the depressive rats the omega-3 fatty acid levels were not decreased, but arachidonic acid was substantially increased as compared to controls is somewhat unexpected," admits Dr. Green. "But the finding lends itself nicely to the theory that increased omega-3 fatty acid intake may shift the balance between the two fatty acid families in the brain, since it has been demonstrated in animal studies that increased omega-3 fatty acid intake may result in decreased brain arachidonic acid."
Especially interesting in terms of the previous uridine/fish oil rat study, isn't it?
If it's arachidonic acid reduction that is significant aside from or in addition to increasing omega-3, then it suggests that if you eat a high animal-fat diet you'd benefit from increasing uridine via magnesium orotate and/or CDP-choline, correct? Is it possible too that if you don't have enough uridine that proper synethesis of phosphatidylcholine is not what it should be? Iow, increasing uridine and thus PC is different from simply ingesting lecithin?
I'm looking up arachidonic acid and see that it promotes inflammation which is also associated with depression.
And according to Dr. Barry Sears, "The higher your insulin levels, the more your body is stimulated to make arachidonic acid." http://www.zonediet.com/free/article.aspx?type=aboutzone&id=005
Hmm...all very intriguing in view of my more unfortunate dietary habits and their obvious link with depression.
JL
Posted by Larry Hoover on May 26, 2005, at 19:16:21
In reply to Re: Magnesium orotate, uridine, arachidonic acid » Larry Hoover, posted by JLx on May 26, 2005, at 12:43:02
Quick comments to your lengthy post.....
I don't think the intention is to get 500 mg/day of elemental magnesium from magnesium orotate supplements, is it? It's to take 500 mg of the complex, which just happens to be mostly orotic acid by mass (orotic acid is a pretty large molecule, and magnesium is a single atom).
Yes, it looks like orotic acid is better than lecithin. And citicholine perhaps better still. That does not mean, however, that the two cannot work together in harmony. If you supply two parallel metabolic pathways simultaneously, you tend to promote those aspects of each pathway (the alternate routes) which are not congruent. So, I'd wager that lecithin plus citicholine is better than just citicholine. Of course, I plan to try it alone, and in concert with fish oil.
The oxidation products of arichidonic acid accidentally formed upon cell death are coincidentally the same ones that are purposely released to signal inflammatory processes. The end result is the same; the arichidonic acid cascade is indeed predominant in depression. Chicken or egg, who knows.
Lar
Posted by JLx on May 26, 2005, at 21:25:31
In reply to Re: Magnesium orotate, uridine, arachidonic acid » JLx, posted by Larry Hoover on May 26, 2005, at 19:16:21
> I don't think the intention is to get 500 mg/day of elemental magnesium from magnesium orotate supplements, is it? It's to take 500 mg of the complex, which just happens to be mostly orotic acid by mass (orotic acid is a pretty large molecule, and magnesium is a single atom).
I was just thinking of 500 mg if one wanted to replace other forms of magnesium with magnesium orotate. You're saying the actual amount of magnesium doesn't matter?
> Yes, it looks like orotic acid is better than lecithin. And citicholine perhaps better still. That does not mean, however, that the two cannot work together in harmony. If you supply two parallel metabolic pathways simultaneously, you tend to promote those aspects of each pathway (the alternate routes) which are not congruent. So, I'd wager that lecithin plus citicholine is better than just citicholine. Of course, I plan to try it alone, and in concert with fish oil.
Lecithin is one thing I'm not sure I have a good result with. It seems like I always end up NOT taking it, if you know what I mean, in kind of a intuitive process. So I wondered if CDP-choline might be different.
> The oxidation products of arichidonic acid accidentally formed upon cell death are coincidentally the same ones that are purposely released to signal inflammatory processes. The end result is the same; the arichidonic acid cascade is indeed predominant in depression. Chicken or egg, who knows.
Yes, that's always the question, isn't it?
JL
Posted by Larry Hoover on May 26, 2005, at 22:47:37
In reply to Re: Magnesium orotate, uridine, arachidonic acid » Larry Hoover, posted by JLx on May 26, 2005, at 21:25:31
> > I don't think the intention is to get 500 mg/day of elemental magnesium from magnesium orotate supplements, is it? It's to take 500 mg of the complex, which just happens to be mostly orotic acid by mass (orotic acid is a pretty large molecule, and magnesium is a single atom).
>
> I was just thinking of 500 mg if one wanted to replace other forms of magnesium with magnesium orotate. You're saying the actual amount of magnesium doesn't matter?Mag orotate isn't a good source of magnesium, but it's a balanced source of the magnesium/orotate that seems to dock best into that enzyme active site. So, more magnesium wouldn't be adverse, and you could certainly get that from your usual citrate/malate/chelate or whatever.
> > Yes, it looks like orotic acid is better than lecithin. And citicholine perhaps better still. That does not mean, however, that the two cannot work together in harmony. If you supply two parallel metabolic pathways simultaneously, you tend to promote those aspects of each pathway (the alternate routes) which are not congruent. So, I'd wager that lecithin plus citicholine is better than just citicholine. Of course, I plan to try it alone, and in concert with fish oil.
> Lecithin is one thing I'm not sure I have a good result with. It seems like I always end up NOT taking it, if you know what I mean, in kind of a intuitive process. So I wondered if CDP-choline might be different.I just found a really cheap source of what is supposed to be the proper lecithin granules. Some are produced by a really inferior process, or something. I'm not sure what I've been getting locally, so I'll compare them.
Or do you use the lecithin oil caps? I don't use those, so maybe we're experiencing different substances/effects?
> > The oxidation products of arichidonic acid accidentally formed upon cell death are coincidentally the same ones that are purposely released to signal inflammatory processes. The end result is the same; the arichidonic acid cascade is indeed predominant in depression. Chicken or egg, who knows.
>
> Yes, that's always the question, isn't it?
>
> JLIn the end, if it makes you feel better, do it again. If it made you feel worse, don't. All the rationalizing in the world won't affect the empirical results.
I'm trying hard to not get too encouraged by the uridine/chronic fatigue link. Finding something that works for chronic fatigue would be a total blessing.
Lar
Posted by Hugh Bristic on November 22, 2005, at 8:26:04
In reply to Re: Where to find, questions....Larry, » Peter S., posted by JLxx on May 4, 2005, at 12:13:54
For those of you thinking of taking citicoline for depression you should consider the following article. Basically, it says that citicoline breaks down into cytidine and choline and that they have antagonsitic effects when it comes to depression, as measured by the forced swim test(FST). Citicoline itself has no effect on the FST, choline decreases the time to immobility (meaning it may actually make you depressed), and cytidine has effects similar to standard anti-depressants. I haven't been able to find cytidine anywhere except at chemical manufacturers and those listings don't appear to be straight uridine, but instead are cytidine-5'-monophosphate and cytidine 5'-triphosphate. Don't know if thats the same as plain old cytidine or not. I think I remeber reading that cytidine turns into cytidine 5'-triphosphate when it crosses the blood brain barrier, but don't quote me. I'm not a scientist, so take what I'm saying with a grain of salt. That is my interpretation of what I've found out though. Looks like the uridine reagent mentioned elswhere in this thread would be your best bet if you want to be risky and experiment on yourself, but I have no idea what the dosage would be for humans or even if it would work taken orally (the mice were given injections, I think).
Antidepressant-like effects of cytidine in the forced swim test in rats
William A. Carlezon, Jr Corresponding Author Contact Information, a, Andrea M. Pliakasa, Aimee M. Parowa, Michael J. Detkea, Bruce M. Cohena and Perry F. Renshawa
a Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts (WAC, AMP, AMP, BMC, PFR) and USA Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana (MJD)
Received 16 August 2001; revised 24 October 2001; accepted 31 October 2001. Available online 14 May 2002.
Abstract
Background: Altered brain phospholipid metabolism may be involved in the pathophysiology of cocaine dependence and mood disorders. Evidence suggests that citicoline, a rate-limiting metabolite for phospholipid synthesis, reduces cocaine craving in human addicts. Because antidepressants can reduce cocaine craving, we explored in rats the possibility that citicoline has antidepressant effects. We also tested the primary metabolites of citicoline, cytidine and choline.
Methods: We examined if citicoline or metabolites alter immobility in the forced swim test. We used two scoring methods: latency to become immobile, a simple method that identifies antidepressants, and behavioral sampling, a complex method that differentiates antidepressants according to pharmacological mechanisms.
Results: Over a range of doses, citicoline did not affect behavior in the forced swim test. At molar equivalent doses, cytidine dramatically decreased immobility, whereas choline tended to increase immobility. The effects of cytidine resemble those of desipramine, a standard tricyclic antidepressant. None of the treatments affected locomotor activity, and cytidine did not establish conditioned place preferences.
Conclusions: Citicoline does not have effects in the forced swim test, but its primary metabolites have opposing effects: cytidine has antidepressant-like actions, whereas choline has prodepressant-like actions. At antidepressant doses, cytidine lacks stimulant and rewarding properties. This is the first report of potential antidepressant effects of cytidine.
Posted by aabag on May 25, 2008, at 20:12:09
In reply to Re: Uridine- Where do I get it? » Larry Hoover, posted by Peter S. on April 10, 2005, at 22:13:03
Thee's a company called Cardiovascular Research Ltd which sells a uridine supplement now. Haven't tried it. Surprised given the Harvard study (http://www.mclean.harvard.edu/news/press/current.php?id=72 ) on uridine antidepressent efficacy that some company didn't immediately come out w/ a uridine supplement. Well, now one has.
This is the end of the thread.
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