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Substances for upregulating dopamine receptors


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#31 golden1

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Posted 20 July 2012 - 12:11 AM

I used it @ 1 dose of 1mg once(I think I am very responsive to it, as I've let friends try and they don't notice 5mg... lol 1mg for me has an obvious efffect(I can also in general take much lower doses of stimulants and get way more intensity than 90% of the people on the internet/bluelight who take like over triple my doses.. but maybe its a bad crowd to compare to.. ha), anyway I only used it once to help with the worst of the withdrawal of amps, then after that dose slowly wore off(~1 week) I was already feeling much closer to normal. It was for me, basically just to make me feel better so the w/d wasn't a problem, not so much to hurry it along, but I doubt it stalled the recovery at all tbh.

#32 mycotheologist

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Posted 20 July 2012 - 09:14 AM

I tried some Emsam (Selegiline Transdermal) today and it seems to have solved the issues I've had after stopping Adderall so far. Thanks for the suggestion. The only concern that I have is the possibility of additional downregulation. Since Selegiline inhibits the breakdown of dopamine and allowing more to be available in the brain, wouldn't this lead to downregulation?

Good to know, thanks for sharing that. I'm gonna try it myself once I've fully recovered from the GABAergic binge I had over the past few months. Right now, opioids make me a bit anxious (which is a sign that I haven't fully recovered) so I'm reluctant to try selegiline just yet in case it causes anxiety due to my partially downregulated GABA system. I wouldn't worry about additional downregulation with selegiline, it should be very minor, if any at all. Its prescribed to people with Parkinsons disease and the last thing they'd need are less dopamine receptors. I'd say it will postpone upregulation though. Like I said, its just for remedying the symptoms. To recover from the downregulation, you can use NMDA antagonists, ibogaine, ayahuasca and other classes of substances. I'd personally only use ibogaine or aya as a last resort though considering the nature and intensity of the effects they induce. Also, I'd wait until the MAOI has completely left your system before taking any NMDA antagonists. Maybe not all NMDA antagonists are have adverse interactions with MAOIs but I read that DXM does. I'd avoid ibogaine at all costs while on an MAOI. As for ayahuasca, you could probably just take the DMT plant by itself without adding an extra MAOI to the mix.

Do any of you have any experience with combining benzos with selegiline? I want to try selegiline ASAP so I'll know if I can depend on it for college next year but if it ends up inducing bad anxiety when I test it out, I'll need a way to counter that since its effects last such a long time (it actually lasts a week?). I have plenty of alprazolam left over at the moment but I'd be worried that it would have a negative interaction with the MAOI. I've looked up interactions between MAOIs and benzos and some people say the combo makes them lethargic but I've never heard anything about selegiline with benzos.

EDIT: According to the people posting on this thread:
http://www.benzobudd...p?topic=46541.0
there are no adverse interactions between selegiline and various benzos so I'm gonna test it out soon. Some people even report that selegiline alleviates their anxiety.

Edited by mycotheologist, 20 July 2012 - 09:46 AM.


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#33 golden1

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Posted 20 July 2012 - 01:16 PM

I tried some Emsam (Selegiline Transdermal) today and it seems to have solved the issues I've had after stopping Adderall so far. Thanks for the suggestion. The only concern that I have is the possibility of additional downregulation. Since Selegiline inhibits the breakdown of dopamine and allowing more to be available in the brain, wouldn't this lead to downregulation?

Good to know, thanks for sharing that. I'm gonna try it myself once I've fully recovered from the GABAergic binge I had over the past few months. Right now, opioids make me a bit anxious (which is a sign that I haven't fully recovered) so I'm reluctant to try selegiline just yet in case it causes anxiety due to my partially downregulated GABA system. I wouldn't worry about additional downregulation with selegiline, it should be very minor, if any at all. Its prescribed to people with Parkinsons disease and the last thing they'd need are less dopamine receptors. I'd say it will postpone upregulation though. Like I said, its just for remedying the symptoms. To recover from the downregulation, you can use NMDA antagonists, ibogaine, ayahuasca and other classes of substances. I'd personally only use ibogaine or aya as a last resort though considering the nature and intensity of the effects they induce. Also, I'd wait until the MAOI has completely left your system before taking any NMDA antagonists. Maybe not all NMDA antagonists are have adverse interactions with MAOIs but I read that DXM does. I'd avoid ibogaine at all costs while on an MAOI. As for ayahuasca, you could probably just take the DMT plant by itself without adding an extra MAOI to the mix.

Do any of you have any experience with combining benzos with selegiline? I want to try selegiline ASAP so I'll know if I can depend on it for college next year but if it ends up inducing bad anxiety when I test it out, I'll need a way to counter that since its effects last such a long time (it actually lasts a week?). I have plenty of alprazolam left over at the moment but I'd be worried that it would have a negative interaction with the MAOI. I've looked up interactions between MAOIs and benzos and some people say the combo makes them lethargic but I've never heard anything about selegiline with benzos.

EDIT: According to the people posting on this thread:
http://www.benzobudd...p?topic=46541.0
there are no adverse interactions between selegiline and various benzos so I'm gonna test it out soon. Some people even report that selegiline alleviates their anxiety.

Yes there is no bad interaction, however if you slide below your threshold dose of benzos(start to slightly w/d) it makes it decently worse...I've never got anxiety from it on or off benzos. The main side effects when they were there were tiredness, senses lacking flair/interest, and not being able to do tons of other drugs hahah.

#34 MrHappy

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Posted 21 July 2012 - 06:37 AM

Inositol increases D2 receptor density.

Up regulating natural dopamine production is just the same as up regulating receptors.
Nicotine and thc long term upregulates dopamine production

It is not the same. If you upregulate production, receptors will downregulate to compensate. You might get a net gain when you reach the new equilibrium, but it's not a sure thing like upregulating receptors through external mechanisms is.

Uridine.

Do you remember the study for this? I thought it only increased neurites and dentrites.


There are some studies in the big thread, but this has a good primer:
http://www.ninds.nih...ine dossier.pdf
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#35 chrisp2

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Posted 22 July 2012 - 04:17 AM

Inositol increases D2 receptor density.


I've been doing a lot of searching, and the only thing I can come up with that seems to upregulate D2 receptors is inositol. And maybe forskolin?

Urdine may increase dopamine levels - thus having the opposite effect of what I'm looking for.

I've seen some comments elsewhere suggesting GABA might help here, but I'm not convinced. Similarly 5-htp, but even less convinced on that.

Ugh. Just trying to find something that can help accelerate the repair of my receptors other than just waiting for them to recover.

Edited by chrisp2, 22 July 2012 - 04:18 AM.


#36 MrHappy

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Posted 22 July 2012 - 07:52 AM

I've been doing a lot of searching, and the only thing I can come up with that seems to upregulate D2 receptors is inositol. And maybe forskolin?

Urdine may increase dopamine levels - thus having the opposite effect of what I'm looking for.

I've seen some comments elsewhere suggesting GABA might help here, but I'm not convinced. Similarly 5-htp, but even less convinced on that.

Ugh. Just trying to find something that can help accelerate the repair of my receptors other than just waiting for them to recover.


It increases receptor densities and *modulates* DA release. Can't see how it wouldn't be ideal for your situation, but ultimately it's your $12 gamble. :)
http://www.swansonvi...rceCode=INTL401

#37 chrisp2

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Posted 22 July 2012 - 01:09 PM

It increases receptor densities and *modulates* DA release. Can't see how it wouldn't be ideal for your situation, but ultimately it's your $12 gamble. :)
http://www.swansonvi...rceCode=INTL401


Modulates meaning, adjust... And if it adjusts it higher, my concern is that the sensitivity of DA neurons does not return to normal.

It is NOT an issue of cost. I'd spend hundreds - thousands to accelerate the repair of what I think might be causing my anhedonia. But I don't want to take something that is going to prolong my situation.

#38 MrHappy

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Posted 22 July 2012 - 01:24 PM

It increases receptor densities and *modulates* DA release. Can't see how it wouldn't be ideal for your situation, but ultimately it's your $12 gamble. :)
http://www.swansonvi...rceCode=INTL401


Modulates meaning, adjust... And if it adjusts it higher, my concern is that the sensitivity of DA neurons does not return to normal.

It is NOT an issue of cost. I'd spend hundreds - thousands to accelerate the repair of what I think might be causing my anhedonia. But I don't want to take something that is going to prolong my situation.


Modulates = regulates
ie. Normalises

#39 golden1

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Posted 22 July 2012 - 03:01 PM

CDP-choline supposedly does its dopamine and other magic through being metabolised to uridine, if I remember correctly, and it only has a positive cumulative effect for me.. nothing negative when stopping or taking for a month. I could try uridine I suppose... has anyone tried both CDP choline and uridine and compare?

#40 MrHappy

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Posted 22 July 2012 - 11:18 PM

Hebbeh has.. and a few others. Uridine is significantly more effective. Perhaps have a read of the big thread. :)
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#41 protoject

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Posted 23 July 2012 - 05:12 PM

CDP-choline supposedly does its dopamine and other magic through being metabolised to uridine, if I remember correctly, and it only has a positive cumulative effect for me.. nothing negative when stopping or taking for a month. I could try uridine I suppose... has anyone tried both CDP choline and uridine and compare?



I have experience with both.. I didn't find much benefit with uridine or triacetyluridine. However my problem is this.. first of all i took these with other supplements. Second of all personally whenever i did take them without other supplements i didn't notice a benefit either,.. however I've been taking the dose of what people in this forum talk about.. some ridiculously low dose.. I bet i'd get more of an effect taking higher doses. Unfortunately I don't know any reliable bulk suppliers, and I ended up getting some triacetyluridine that is like 20 ppm of heavy metals and it tastes like drywall so i decided not to use it anymore.

#42 golden1

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Posted 23 July 2012 - 08:58 PM

I'lll stick to CDP-Choline, hahahah. thanks for the input

#43 gizmobrain

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Posted 23 July 2012 - 11:02 PM

Sticking some Uridine-5'-monophosphate disodium (UMP) from Superior Nutraceuticals under my tongue actually has a psychoactive effect after a few minutes. It's effects "feel" different depending on what other noots I have running around in my body at the time.

If I take it first thing in the morning with nothing else, I feel more awake and alert. However, the other day, I had taken too many stimulants, and it helped me calm down.

#44 golden1

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Posted 23 July 2012 - 11:29 PM

Hmm very very similar to cdp-choline(taken with nothing else will add energy/focus, taken with stimulant enhances the effect and dulls the negatives of the stimulant really well, I take 250-500mg CDP CHOLINE), thank you for the info. I was wondering how much UMP that was that you took zrbarnes? So I could see if its a logical scale up to my dose of cdp-choline's uridine content(when mathed out with molar weights or whatever the technical terms are)

#45 Hebbeh

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Posted 24 July 2012 - 12:24 AM

Sticking some Uridine-5'-monophosphate disodium (UMP) from Superior Nutraceuticals under my tongue actually has a psychoactive effect after a few minutes. It's effects "feel" different depending on what other noots I have running around in my body at the time.

If I take it first thing in the morning with nothing else, I feel more awake and alert. However, the other day, I had taken too many stimulants, and it helped me calm down.


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#46 Hebbeh

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Posted 24 July 2012 - 12:27 AM

Hmm very very similar to cdp-choline(taken with nothing else will add energy/focus, taken with stimulant enhances the effect and dulls the negatives of the stimulant really well, I take 250-500mg CDP CHOLINE), thank you for the info. I was wondering how much UMP that was that you took zrbarnes? So I could see if its a logical scale up to my dose of cdp-choline's uridine content(when mathed out with molar weights or whatever the technical terms are)


CDP is nice but sublingual UMP is a whole different ball game. It's my number 1 must have supp now. Although I'm working on C60 pretty seriously.

#47 Raza

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Posted 25 July 2012 - 07:01 PM

Inositol increases D2 receptor density.

Up regulating natural dopamine production is just the same as up regulating receptors.
Nicotine and thc long term upregulates dopamine production

It is not the same. If you upregulate production, receptors will downregulate to compensate. You might get a net gain when you reach the new equilibrium, but it's not a sure thing like upregulating receptors through external mechanisms is.

Uridine.

Do you remember the study for this? I thought it only increased neurites and dentrites.


There are some studies in the big thread, but this has a good primer:
http://www.ninds.nih...ine dossier.pdf

Right, it speeds up a return to baseline levels of dopamine levels and receptors both, after up/down regulation by antagonists by increasing receptor turnover, kind of like speeding up your brain's metabolism in general.

So that's good for the OP or resolving dependency/tolerance, but bad when you're making a targeted effort to increase receptors above baseline through chronic treatment with things like Inositol, Forskolin, CDP or Phenylpiracetam.

Which is a lot like the effect of NMDA receptor antagonists, but slightly different in that those are only known to induce receptorgenesis, and not downregulation to baseline, as far as I know. (not certain of this at all, I just haven't heard of them quickening downregulation after treatment with an antagonist)

Edited by Raza, 25 July 2012 - 07:09 PM.


#48 MrHappy

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Posted 25 July 2012 - 09:21 PM

Right, it speeds up a return to baseline levels of dopamine levels and receptors both, after up/down regulation by antagonists by increasing receptor turnover, kind of like speeding up your brain's metabolism in general.

So that's good for the OP or resolving dependency/tolerance, but bad when you're making a targeted effort to increase receptors above baseline through chronic treatment with things like Inositol, Forskolin, CDP or Phenylpiracetam.

Which is a lot like the effect of NMDA receptor antagonists, but slightly different in that those are only known to induce receptorgenesis, and not downregulation to baseline, as far as I know. (not certain of this at all, I just haven't heard of them quickening downregulation after treatment with an antagonist)


Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.

Trying to increase D2 receptors above a 'normal' baseline with any substance is like beating your head against a wall, owing to homeostatis. Your body will rebalance the equation, one way or another, every time.

However, if you are starting from below what your normal baseline should be, you'll be a happy camper. This is why uridine is so effective with bipolar disorder.
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#49 chrisp2

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Posted 26 July 2012 - 11:40 AM

Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.

Trying to increase D2 receptors above a 'normal' baseline with any substance is like beating your head against a wall, owing to homeostatis. Your body will rebalance the equation, one way or another, every time.

However, if you are starting from below what your normal baseline should be, you'll be a happy camper. This is why uridine is so effective with bipolar disorder.


Agreed that the body will recover on it's own.

Provided DA2 levels come down by abstaining from whatever activity drove them high... Food, drugs, orgasm, etc.

I am however looking to understand what may help my body in this recovery.

Right now I'm taking inositol. Some indications of improvement but it very well could be anecdotal.

I decided to stay away from Forskolin, as I saw a study that suggested it also increased DA levels. (Other published accounts do suggest it upregulated receptors, but if I'm going to work hard to keep my DA levels down (well, at least not have them artificially high) over the next 2+ months, I don't want to do anything that may sacrifice my recovery.

#50 MrHappy

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Posted 27 July 2012 - 08:02 AM

Well, see how you go with inositol, but perhaps keep this in mind in case you aren't making progress with it.

I know from personal experience how uridine works and I'm 99.999% sure it'll do exactly what you need. It acts like a DA clamp to baseline (the more you take, the bigger the clamp) and accelerates the recovery/rebalance process.

Anyway, good luck, whatever you do! :)

#51 Raza

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Posted 28 July 2012 - 09:09 AM

Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.

That sounds likely, actually. Good to know.

Trying to increase D2 receptors above a 'normal' baseline with any substance is like beating your head against a wall, owing to homeostatis. Your body will rebalance the equation, one way or another, every time.

Hmm, I don't agree. Any substance that increases (rather than normalizes, which can be difficult to distinguish) receptor density by means other than lowering ligand availability should give a net gain against homeostasis. Raising ligand levels reduces receptors, but that doesn't work the other way around except to a small extend for autoreceptors.

Plus, there's the way that everyday baseline receptor density is still lowered by everyday baseline ligand levels. Depending on whether uridine and/or NMDA antagonists speed up receptorgenesis towards current targets adjusted for active ligand activity or towards 'default' levels under zero ligand activity, they could still help increase receptor density above the everyday baselines we're used to in real-life situations.

Edited by Raza, 28 July 2012 - 09:17 AM.


#52 chrisp2

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Posted 28 July 2012 - 03:28 PM

Well, see how you go with inositol, but perhaps keep this in mind in case you aren't making progress with it.

I know from personal experience how uridine works and I'm 99.999% sure it'll do exactly what you need. It acts like a DA clamp to baseline (the more you take, the bigger the clamp) and accelerates the recovery/rebalance process.

Anyway, good luck, whatever you do! :)


Thank you :)

I haven't quite proven a causative effect through any studies, but one symptom of my anhedonia has been the lack of dreams - at least dreams that I recall upon waking.

I seem to be having more since starting inositol and choline in high doses (out of the "mix" now trying just inositol)... And I seem to be waking with erections more often.

It's all anecdotal at this point, could be placebo effect - although it would have to be subconscious. If it continues, I'll be more confident that it is not a random "blip", but maybe finally after years of struggle that I have latched onto the true cause.

If you don't mind, I'd like to hear more about your personal experience. Does that super long thread have a particular post that tells your story, and your recovery?

Thanks again...

#53 protoject

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Posted 28 July 2012 - 05:16 PM

I think homeostasis and baseline are pretty tricky things though. Baseline does change from time to time. Though I'm not sure how it gets to the level that it does exactly. my 'baseline' is different from what it was 5 years ago or even one year ago. Why's that? What causes the deviation? Seems like deviation is able to be maintained within a certain range. And homoeostasis isn't perfect. Though it works pretty damn well.

#54 tritium

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Posted 28 July 2012 - 11:21 PM

I hope, in the future, that scientists will discover a chemical which has the ability to inhibit homeostasis, specifically in regard to dopamine receptors. It is this homeostasis which holds many people back from becoming geniuses, but instead it brings them back down to their dumber level.
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#55 MrHappy

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Posted 29 July 2012 - 12:00 AM

My story is probably quite typical.

High pressure job - emergency environment problem solving and constant 14-16 hour days. After 10 years at this level of stress, I had been finding myself losing my edge and my ability to cope. It was getting harder to get out of bed in the morning. I was burnt out and turning into a shell of a zombie - something needed to change.

After doing some research and starting on that combination of nutrients, the difference was like night and day.

My stress levels disappeared.
My mood improved.
My sleep improved.
My eyesight improved - only while supplementing.
Most importantly, my cognitive function returned to normal and subjectively, eventually improved above my previous level.
I had my life back. I was back! Feels good! :)

The best part - most of these improvements stayed long after supplementing. The eyesight improvements require daily supplementation to maintain. There are other mitochondrial benefits, so I'm happy to do so.

Over the last 9 months, I've had the opportunity to continue journal research, as well as experiment with doses, complete breaks, variations, etc. and combined with the Imminst community experiences, I feel that we have a good working understanding. We are always learning and that's the way it should be. :)
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#56 MrHappy

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Posted 29 July 2012 - 12:08 AM

I hope, in the future, that scientists will discover a chemical which has the ability to inhibit homeostasis, specifically in regard to dopamine receptors. It is this homeostasis which holds many people back from becoming geniuses, but instead it brings them back down to their dumber level.


It's not all about dopamine, though.
Growth factors - NGF, BDNF, GDNF, etc.

There appears to be a way to stop homeostatis for these factors, involving upregulating TrkA, TrkB, TrkC while increasing the growth factors. This hasn't been throughly explored, yet.

#57 protoject

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Posted 29 July 2012 - 01:40 AM

My story is probably quite typical.

High pressure job - emergency environment problem solving and constant 14-16 hour days. After 10 years at this level of stress, I had been finding myself losing my edge and my ability to cope. It was getting harder to get out of bed in the morning. I was burnt out and turning into a shell of a zombie - something needed to change.

After doing some research and starting on that combination of nutrients, the difference was like night and day.

My stress levels disappeared.
My mood improved.
My sleep improved.
My eyesight improved - only while supplementing.
Most importantly, my cognitive function returned to normal and subjectively, eventually improved above my previous level.
I had my life back. I was back! Feels good! :)

The best part - most of these improvements stayed long after supplementing. The eyesight improvements require daily supplementation to maintain. There are other mitochondrial benefits, so I'm happy to do so.

Over the last 9 months, I've had the opportunity to continue journal research, as well as experiment with doses, complete breaks, variations, etc. and combined with the Imminst community experiences, I feel that we have a good working understanding. We are always learning and that's the way it should be. :)

yep that's what i love! say, when do you think your journey began? how long ago? mine began several years ago and i'm beginning to believe its going to pay off.

#58 chrisp2

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Posted 29 July 2012 - 07:26 PM

After doing some research and starting on that combination of nutrients, the difference was like night and day.


What nutrients? Just Urdine, or other stuff too?

#59 Hebbeh

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Posted 29 July 2012 - 07:48 PM

After doing some research and starting on that combination of nutrients, the difference was like night and day.


What nutrients? Just Urdine, or other stuff too?



http://www.longecity...ne-uridine-dha/

It's all in the 42 pages. I'm suprised you haven't read it yet.

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#60 chrisp2

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Posted 30 July 2012 - 12:10 AM

http://www.longecity...ne-uridine-dha/

It's all in the 42 pages. I'm suprised you haven't read it yet.


Well I have, sort of.

Just the problem - other than the length, is understanding all aspects of what is being discussed.

You throw those two things together, and for a non-expert (not a novice really), well it's just tough on the overall comprehension.




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