2844 replies to this topic

[MrHappy]

Just aim for mixed tocopherols iHerb has a few.

[choqueiro]

No response yet.

I´m start thinking in this causes:

1) Excess of choline. Maybe as JChief suggested my brain fog is caused by Alpha GPC (I think it gets worse after taking all the cofactors). I don´t know if reduce quantitie, take ALCAR instead or directly don´t take choline.
2) Fish oil. Even though Omega 3 it is said to be a good supplement not every fish oil and not all quantities may be good. Rigt now I´m taking daily 1.800 mg of DHA and 360 mg. of EPA. I don´t kow what to do. More EPA?? Only EPA?? Avoid fishoil?
3) Uridine: I don´t know if my actual dose (250 mg. daily) it´s enough. Maybe it also be good try TAU instead of UMP. Any opinion??
4) Maybe I´m a non responder.

[nupi]

can anyone advise me on which vitamin E to buy?

i'm thinking jarrows famliE or jarrows gamma 300? (AOR too expensive for my current budget)

From my brief research 2 weeks ago, http://www.iherb.com...ftgels/523?at=0 seemed like a decent deal. Research is somewhat complicated by the fact that most of them do not really tell you the ratios of the individual tocopherols :(

[csrpj]

i'm thinking of going w/: http://www.iherb.com...20-Softgels/205

it's good?
how much to take per day?
(also - i'm sure this is my OCD talking but bear with me - if i'm taking this with fish oil and and trying to time it together.... if my fish oil is liquid i take in directly, and these vitamin e pills take time for their coating to dissolve, is this not a problem?)

[rg8032]

[...]if my fish oil is liquid i take in directly, and these vitamin e pills take time for their coating to dissolve, is this not a problem?)

Fish oil should be taken with a meal. Its bioavailability will increase from ~20% to ~60% or ~70% to 90% for ethyl ester and natural triglyceride forms respectively. When taken with a meal, the slightly delayed release of the encapsulated supplement becomes meaningless as digestive processing takes longer with a gut full of food.

My guess is that you could dose the supplements 12 hours or more apart and not notice a difference.

[MrHappy]

Choqeiro - try halving the fish oil or even don't take it for a few days. If that's still an issue, try either stopping alpha-gpc or switching to ALCAR.

I have also heard of very rare cases where vitamin B can cause brain fog.

[csrpj]

what about the timing of the uridine and choline.... can the choline source be taken at a different time of the day from uridine?


PS: today is my third day on the uridine combo. i'll wait maybe 10 days before drawing initial conclusions. i sincerely hope this will allow me to deal with some of the demons i've been struggling with, though i'm staying quite caustious when it comes to this type hope.

anyway, i'm taking 75 TAU.

i'm also taking ALCAR as my choline source: how much should i take?

i have all co-factors in my system (E, Bs), and for fish oil, i'm taking 1230/822 EPA/DHA. (does time-of-day for fish oil matter?)

i also hope with this stack, i can follow in you're wife's footsteps, mr happy, and taper off from zoloft! (which isn't helpingsubstantially, and is contraindicated with some treatments i want to explore)

Edited by csrpj, 06 February 2012 - 03:18 PM.

[rg8032]

Post numer 795 and post number 800 just made it out of the moderation queue. Some of you might find this interesting. Especially post 800 which deals with the probable myth of caffeine-and-nicotine-induced bioavailability reduction.

[rg8032]

Post numer 795 and post number 800 just made it out of the moderation queue. Some of you might find this interesting. Especially post 800 which deals with the probable myth of caffeine-and-nicotine-induced bioavailability reduction.

[rg8032]

what about the timing of the uridine and choline.... can the choline source be taken at a different time of the day from uridine?
[...]
i'm also taking ALCAR as my choline source: how much should i take?
[...]
does time-of-day for fish oil matter?
[...]

First off, ALCAR (acetyl L-carnitine) is not a choline source. It can provide a boost to acetylcholine (ACH) amongst other things, but it is not choline nor is it convertible to choline. ALCAR can donate its acetyl group to a number of biological processes (e.g. to make Acetyl-Coenzyme A). In order to create ACH, an acetyl group is joined with choline to make ACH. ALCAR can supply this acetyl group.

If I wanted to to make unsubstantiated claims, I might conjecture that ALCAR increases choline requirements and that this extra choline comes from dietary choline intake or from robbing membrane phosphocholine. These choline-sourcing mechanisms are real, but whether this occurs with ALCAR supplementation and to what degree I can not comment.

The relative timing of your doses are probably not hugely important. As a general rule, water-soluble supplements do better when taken on an empty stomach, whereas fat-soluble supplements are better taken with a fat-containing meal. TAU is fat soluble. ALCAR is water soluble.

Take fish oil at any time. Depending on the form the fish oil is in, you can double or almost quadruple the bioavailability of fish oil by taking it with a fatty meal. Many lipid-soluble supplements have a tendency to be stored efficiently by the body (e.g. vitamin D can be taken once daily or once weekly at seven times the daily dose). I imagine that fish oil is affected similarly.

Edited by rg8032, 06 February 2012 - 04:27 PM.

[rg8032]

Double post. Itchy trigger finger.

Edited by rg8032, 06 February 2012 - 04:20 PM.

[csrpj]

so with the timing...

what about the timing of the uridine and choline.... can the choline source be taken at a different time of the day from uridine?
[...]
i'm also taking ALCAR as my choline source: how much should i take?
[...]

First off, ALCAR (acetyl L-carnitine) is not a choline source. It can provide a boost to acetylcholine (ACH) amongst other things, but it is not choline nor is it convertible to choline. ALCAR can donate its acetyl group to a number of biological processes (e.g. to make Acetyl-Coenzyme A). In order to create ACH, an acetyl group is joined with choline to make ACH. ALCAR can supply this acetyl group.

If I wanted to to make unsubstantiated claims, I might conjecture that ALCAR increases choline requirements and that this extra choline comes from dietary choline intake or from robbing membrane phosphocholine. These choline-sourcing mechanisms are real, but whether this occurs with ALCAR supplementation and to what degree I can not comment.

The relative timing of your doses are probably not hugely important. As a general rule, water-soluble supplements do better when taken on an empty stomach, whereas fat-soluble supplements are better taken with a fat-containing meal. TAU is fat soluble. ALCAR is water soluble.

so about the timing, i'm wondering if i should shoot for ALCAR empty stomach, then 30min later eat food and take TAU? that's the best i could do for timing give their respective solubility... but that versus a 4 hour gap, say - does it make a difference in the overall effectiveness of the uridine/choline/dha stack?

and about ALCAR not being choline... does one serve themselves short of the uridine/choline/dha benefits by replacing choline for ALCAR, or does it serve a similar purpose and thus a suitable substitute?

[rg8032]

so about the timing, i'm wondering if i should shoot for ALCAR empty stomach, then 30min later eat food and take TAU? that's the best i could do for timing give their respective solubility... but that versus a 4 hour gap, say - does it make a difference in the overall effectiveness of the uridine/choline/dha stack?
...

The timing will not make much of a difference. If you notice an acute energizing effect from either supplement, you should avoid taking it later in the day.

...
and about ALCAR not being choline... does one serve themselves short of the uridine/choline/dha benefits by replacing choline for ALCAR, or does it serve a similar purpose and thus a suitable substitute?

It is hard to say. A few people have been representing this stack as something it is not. What it is not is well understood. One of the mechanisms being advanced as the possible driving force of this stack is the repair of cell membranes in the brain. This requires uridine, choline, and DHA. You can consume any of these three or none of them and the process will still take place varying only in degree.

No studies have been done on the effectiveness of ALCAR vs. choline in this stack so I can not say with any degree of certainty. A few studies show improvements in rats when supplemented with uridine and DHA (I believe there was no choline in some of these studies). To venture a guess, ALCAR may exert its own nootropic effect, but it may be either counter-productive or non-synergistic to the uridine/DHA/choline (i.e. ALCAR may produce no synergistic effect or exert a negative synergistic effect). This is all conjecture. No one can substantiate an answer to this question yet.

If you would like I could explain why exactly ALCAR could be detrimental to the stack. I am not claiming that ALCAR will make the stack ineffective. ALCAR may produce a better outcome when coupled with the stack, but the net effect of the uridine/DHA/choline stack may be reduced in the presence of ALCAR.

If you do better with numbers, the following gives a kindergarten walkthrough of the possible interaction. Numbers were chosen at random. Assume that ALCAR produces a nootropic effect with magnitude 5 and u/d/c produces a nootropic effect with magnitude 7. If ALCAR keeps shunting choline from phosphocholine into acetylcholine (ACH) due to increased ACH synthesis and a lack of dietary choline then it may reduce the net effect of u/d/c by 2. The result could be an overall net effect of 10 instead of 12.

http://wurtmanlab.mi...ic/pdf/1037.pdf
Page 2 top left gives a diagram of what is happening in the u/d/c stack.

It is important to note that the theories professed above could be total bs. They are mostly the unsubstantiated connecting of dots.

Edited by rg8032, 06 February 2012 - 05:10 PM.

[MrHappy]

Rg8032 - sorry I hadn't replied, I think a number of your posts were caught up in a spam/mod filter or similar - I've only just seen them!

I base my reasoning for including Vitamin E off the patent specifications and the commercial product, Fortasyn Connect. Likewise, the B vitamins are also included in 3 commercial uridine-based cognitive products. Logically, I can see the need for both groups of nutrients in this scenario, as both are essential building blocks - one for methylation and the other for lipid membranes. The vitamin E will also act as an antioxidant and should be helpful with the fish oil doses being discussed. B vitamins are useful as uridine appears to accelerate DNA methylation and methylfolate is required to prevent substitution of thymine for uridine during transcription.

I also think the nutrients in breast milk are another indication of possible requirements for this protocol, suitably modified for an older consumer.

Most of my opinions are usually based off a combination of personal experience and earlier citations (particularly when I don't bother to re-qualify them or include another citation). I hope they will be easy to interpret as such - they usually include language such as 'think', 'try', 'should', 'perhaps', 'appear' and 'maybe'. Being that this is a new topic and much of this thread is speculation and experimentation, you'll find a lot of them!

As for nicotine and caffeine, apart from the quoted paper and another patent (that used uridine and adenosine as a stop-smoking aid), we have a few personal accounts, myself included, that demonstrate some typically unwanted interactions with those 2 stimulants. From subjective experiences, it would appear that the same receptors are being used. That AMPA & NMDA calcium signalling paper also provided some very helpful clues, particularly when you read these:
http://www.ncbi.nlm....ubmed/18579301/
http://www.ncbi.nlm....ubmed/18418357/

Thanks for your very helpful input and I'll look forward to seeing how you go.

Edit:typo

Edited by MrHappy, 06 February 2012 - 10:26 PM.

[rg8032]

I believe that it is very possible for uridine to interact with caffeine and nicotine. I just see no evidence for contraindicating the two. No evidence has been presented to support the idea that uridine loses efficacy when administered with nicotine. I have not smoked in years and can not add any anecdotal evidence regarding the subjective effects of co-administration of uridine and nicotine.

http://www.ncbi.nlm....pubmed/18313046

In the present study, we investigated the cardiovascular effects of intravenously injected uridine or cytidine, and the role of adenosine receptors in mediating these effects, in conscious normotensive rats.

Intravenous (i.v.) administration of uridine (124, 250, 500 mg/kg) dose-dependently decreased arterial pressure and heart rate.

[...]

Pretreatment with intravenous caffeine (20 mg/kg), 8-phenyltheophylline (8-PT) (1 mg/kg), nonselective adenosine receptor antagonists, or 8-p-sulfophenyltheophylline (8-SPT) (20 mg/kg), a nonselective adenosine receptor antagonist which does not cross the blood-brain barrier, abolished the cardiovascular effects of uridine (250 mg/kg; i.v.)

[...]

The hypotensive effects of uridine seem to be prevented when caffeine is pre-administered in rats. There is obviously some sort of interaction between the two. It is likely mediated by actions at the adenosine receptors (caffeine is a non-selective adenosine antagonist). The study concluded that uridine acts peripherally on the adenosine receptors. I have had some caffeine (anhydrous, 66mg) and noticed no difference subjectively, but that means nothing.

Intracerebroventricular (i.c.v.) caffeine (200 microg) or 8-SPT (50 microg) pretreatment did not change the magnitude of the cardiovascular responses induced by nucleosides.

Antagonizing receptors in the brain had no effect on uridine's hypotensive effects.

I would be interested to see what the equivalent doses of caffeine and uridine in humans would be. Interaction between caffeine and uridine seems to be real; however, I have only uncovered cardiovascular interaction at peripheral sites. I have seen no evidence to suggest that the effects this thread seeks would be prevented or greatly attenuated by the co-administration of the two.

Thanks for being a sport. I look forward to duking it out in the future.

[rg8032]

My posts keep getting caught up in a moderation queue. Hopefully that stops soon. I heard a rumor that the magic number is between 9 and 11 posts. I replied. If it is not up by tomorrow, I will up my post count and repost. If you want, I can PM you the message that will appear above so you may reply.

I would like to clarify my position on the stated uridine/DHA/choline co-factors. In a min/max'ing sense, I believe that their supplementation will be beneficial. It's my opinion that the difference will probably not be significant. Supplementation with the co-factors is probably a good idea, but I do not believe it to be necessary for an effect. Also, diet quality and co-factor supplementation benefit are likely inversely proportional. As a perfectionist, I choose to take them.

Slightly off topic:
My bottle of Ortho Core labels its folic acid as "folate". Any idea exactly what this means? It lists it as "5-methyltetrahydrofolate" on their website, but the product codes are different. I am assuming I have an old batch. Can anyone clarify?

Edited by rg8032, 07 February 2012 - 01:04 AM.

[JChief]

ALCAR, uridine & DHA all work great. 500mg of ALCAR on empty stomach twice per day. If I take double the dose of ALCAR I get a bit anxious. I have ALCAR in my stack for many reasons...

[MrHappy]

Folic acid is the synthesised version of folate. Methyltetrahydrofolate is an extremely bioavailable version of folate - very nice.

[csrpj]

how long did it take you responders to feel something significant? i'm on my 5th with no effect, and want to map out when i should feel something significant or start concluding i'm a non-responder.

[penisbreath]

Is it possible to see benefits from Uridine without DHA? I'm trialing an MAOI (Parnate) at the mo' which is wrecking havoc on my sleep. I'd like to try Uridine to offset the cognitive sx. of insomnia, but the Parnate is quite stimulating and I find I tend to get anxious on fish oil alone, so would rather not introduce any DHA sources at this stage in the trial.

[MrHappy]

csrpj - at least 10 days before you'd look at adjustments. What's your current stack, etc?

lucky.pierre - see how you go, I find that without DHA, it's somewhat less effective, but certainly still very helpful.

[MrHappy]

Side note: my stock of alpha-gpc is getting low.
Picked up some orange-flavoured ALCAR powder on the way home today.
Going to perform some personal tests on ALCAR in my stack as a comparion to alpha-gpc, since it has worked well for JChief and others.

[penisbreath]

lucky.pierre - see how you go, I find that without DHA, it's somewhat less effective, but certainly still very helpful.

thanks, i'll give it a shot. do you know if uridine is safe to combine with an irreversible maoi?

[MrHappy]

It'll modulate dopamine release, but I'd still take it gently and see how you go.
http://docs.docstoc....a223d245da5.pdf
(see table on the last page and and explanation of the groups in the top right of the previous page)

[penisbreath]

so no effect on serotonin as far as you're aware?

[csrpj]

csrpj - at least 10 days before you'd look at adjustments. What's your current stack, etc?

morning empty stomach:
ALCAR 500mg (and maybe another time around noon)

after breakfast:
TAU 75mg
fish oil (yielding 1230mg/822mg EPA/DHA)
vitamin E (one of these: http://www.iherb.com...20-Softgels/205)
B-vitamins

others not directly related to the stack:
zoloft 75mg (around noon, though i'd love uridine to work so i can begin tapering off zoloft)
magnesium taurate 125mg (at night)
zinc 20mg (at night)
BCAA PRN for weightlifting
creatine PRN for weightlifting

Edited by csrpj, 09 February 2012 - 06:00 PM.

[rogerthat]

Effect of uridine of presynaptic NMDA and kainate receptor of rat brain cortex
Bulletin of Experimental Biology and Medicine (March 2008), 145 (3), pg. 320-322

It was demonstrated that uridine affects presynaptic NMDA and kainite receptors of rat brain cortex. Uridine considerably inhibited ⁴⁵Ca²⁺ uptake into synaptoneurosomes (IC₅₀=7.1×10⁻¹² M) under conditions NMDA stimulation and increased it under conditions AMPA stimulation (157.8%).

Any thoughts how this might interact with stimulants? Particularly Adderall/Dexedrine?

I am taking Lithium Orotate to reduce amphetamine tolerance rising and am a little concerned that tolerance may increase at a faster rate.

Rogerthat - I'd think you'd be able to take roughly 60% less adderall and possibly still get the same effects.

Wouldn't I want to reduce Ca2+ influx at all times though?

I would have thought preventing transient spikes, etc., would be the issue, not normal signalling?

First, let me say I am quite reliant on my Lithium (10mg or so) to stay calm and non-manic (with depressive rebounds). This is ever since I ran in to some major troubles with Phenibut.

After around a week or so of taking Uridine 500mg sub. I ended up taking an "emergency" walk outside my house so that I could be around someone in case something happened. Not really sure what caused it, the only combination I can think of would be Pregnenolone (which I was unaware till today is an NMDA agonist/ mild GABA-A antagonist apparently) and the increasing concentration of Uridine. I had not taken the Dexedrine that day. It happened about 20 mins after my night time Uridine dose. I had symptoms somewhat akin to mild serotonin syndrome or low GABA levels -> a,k,a feeling agitation, depersonalized, hypervigilant, racing heart and so on (no dialted pupils though). As I said though, not sure the cause, but does seem likely Uridine contributed given the timing of it, and that I haven't had anything of the like since stopping the Uridine.

I don't intend to insinuate that Uridine is necessary harmful in anyway, as this is not the first time I have had such an episode (2-3 times since my Phenibut withdrawal for various reasons). It does, however, push me towards extra diligence in regards to it's pharmacokinetics. I wan't to give Uridine another shot later on but only when I better understand the interactions with my particular brain.

Anyways figured I would make a note of it since we are somewhat lacking in anecdotal reports. Other than that episode, I remember being more "awake" in a sense; at the expense of increased anxiety. That's what led me to believe in might be interacting with the NMDA antagonism of the Lithium.

Edited by rogerthat, 09 February 2012 - 10:23 PM.

[truboy]

Guys what time do you take uridine? alexd in his thread

http://www.longecity.org/forum/topic/41790-uridine-and-bi-polar-depression/page__view__findpost__p__414613

saying that urine much more effective before bed.

[MrHappy]

Csprj - maybe the SSRI is masking effects. Keep us posted.

Rogerthat - Very interesting! Sounds like a balancing act for you.. Big questions - how did you come to the 500mg sublingual UMP dose? Last time I tried that dose level, for science, I had some pretty entertaining diarrhea. Also, for what specific benefits are you on adderall and what dose?

[MrHappy]

Truboy - I've tried both ways and I thought the morning dose was better, but maybe I'll try it again the other way for a week.