271 replies to this topic

[CIMN]

Found a study which seems to argue that D-serine and/or Glycine are competitive agonists with regards to another compound at the glycine binding site.

What other compound you ask? Believe it or not: Piracetam.

A potentiation of response to glutamate and aspartate through the glycine site of the NMDA receptor by piracetam has been reported in a Russian study. Another study showed that piracetam and aniracetam at 100 PM do not affect MK-801 binding in the presence of NMDA and glycine. If piracetam acts on the glycine regulatory site of the NMDA receptor the presence of glycine could obscure the potentiating effect of piracetam.

In theory this doesn't make any sense. Glycine and/or D-serine are necessary co-agonists at the NMDA receptor site.

so does that mean it is beneficial or negative?
they say it would obscure the effect of piracetam.

[unbeatableking]

My initial reaction to D-Serine is not good. Maybe the lack of sleep is getting to me so take it with a grain of salt.

D-serine is making me sleepy! Yesterday late afternoon I tried 1.5 grams on an empty stomach and felt a little light headed the rest of the day.

This morning I dropped down to 1g and I feel drained. I went for my normal 5 mile run and it felt terrible. No positive effects noticed.

I think I'm going to give this a break for a few days and try again.

Went through the same thing. I apologize for not having advised you much earlier. :(

[unbeatableking]

@CIMN

Here's the thing. Glycine and/or D-Serine are necessary metabolites at the NMDA channel.

They are the fuel inside of the car, so to speak. Without them, the NMDA channel will not open.

What is odd is that article is pre-supposing that the presence of glycine can potentially obscure the positive effects of Piracetam, by competing at the same binding site, the same keyhole, so to speak.

But that doesn't make any sense. If Piracetam were to replace glycine at its binding site, then theoretically, the NMDA channel should not open, because like I said, glycine and/or D-serine are necessary co-agonists.

So theoretically, taking Piracetam should lead to a decrease in cognitive performance.

Edited by unbeatableking, 14 September 2012 - 05:07 AM.

[health_nutty]

You did! Your posts are a big help I just didn't check the thread one last time before ordering.

Did you find any dose that works? You mentioned Sarcosine has synergy with d serine. Is the combo better than Sarcosine alone?

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[unbeatableking]

^

In theory they shouldn't syngerize, given the fact that they bind to the same binding site.

I have also tried taking both at the same time. Although Sarcosine did deminish the negatives brought upon by D-serine, I felt that Sarcosine alone gave a much better effect.

A dose that works for Sarcosine you mean? 2 grams every 3 hours.

I am still going to look into the purported synergy between Piracetam and Sarcosine. The evidence however, seems to suggest that there isn't.

[CIMN]

@CIMN

What is odd is that article is pre-supposing that the presence of glycine can potentially obscure the positive effects of Piracetam, by competing at the same binding site, the same keyhole, so to speak.
But that doesn't make any sense. If Piracetam were to replace glycine at its binding site, then theoretically, the NMDA channel should not open, because like I said, glycine and/or D-serine are necessary co-agonists.

So theoretically, taking Piracetam should lead to a decrease in cognitive performance.

perhaps irish MD could answer about this, seems he would know more.
anyways it seems best we could do is use anecdotal evidence as to whether piracetam interferes or is beneficial.. bit strange though.

[unbeatableking]

Taking it without Piracetam.

Sarcosine on its own. Will report back later.

[unbeatableking]

Here are some notes (NOTE: I will refer to the triad of Glycine agonists using the acronym GDS):

1. We should not supplement D-Serine and Sarcosine together. They compete with one another in an inhibitive fashion on the same binding site

2. All allosteric modulators have a binding site. A Russian study has hypothesized that Piracetam's binding site on the NMDA receptor may be the Glycine receptor site. This has huge implications. This means that Piracetam may be in itself a competitive agonist. GDS is necessary for the conductance of NMDA receptors, the lack of which will prevent the NMDA receptor from opening.

If Piracetam does indeed exert its effect on the NMDA receptor by binding with the Glycine receptor site, then hypothetically, one should not co-supplement with the two.

Do note that this is one study.

3. Sarcosine seems to be the better choice. The more cost-effective choice that is.

[unbeatableking]

I hope you guys can benefit from my posts.

I have benefited from many other posts on this forum, I hope to be able to contribute, to the best extent that I can possibly do so.

Are there any questions about the stack in question? I can confirm that the stack does indeed have a positive effect on both mood, energy and to some extent - memory..

[health_nutty]

I'm wondering if 1g of d-serine it's too high for me. Before I give up I'll try 500mg and 250mg.

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[unbeatableking]

^

Please do. :D

I have to admit. Given that I have responded positively to Phosphatidylserine, a substance that requires enzyme-mediated conversion in order to become D-serine (meaning that very little of it actually becomes D-serine), one can only speculate if we are taking too much of the metabolite.

This is a good idea. Please report back when you can. :D

[unbeatableking]

Theoretically there is some evidence to suggest that D-serine might have a connection with GABAergic receptors:



Moreover, most of D-serine-positive neurons were GABAergic (98%), underwent degenerating death (93%), and were accompanied enhancing phosphorylation of NMDA receptor subunit 1. This study has provided new evidence that up-regulation of D-serine production might induce GABAergic neuronal degeneration through excitotoxic mechanism in the pilocarpine model and may be involved in early pathogenesis and recurrent seizure of chronic epilepsy.

[health_nutty]

I'm giving 250mg of d-serine a try today. No grogginess, but I am getting irritibility (much like Piracetam does to me). I noticed this last night as well, but now I can see the effect is consistent. I'm hoping it was just the previous high doses lingering.

I'm going to take the weekend off and try 250mg again on Monday as a last ditch effort. If I get irritibility again, I'm going to ditch it.

[unbeatableking]

^

How is it from a cognitive perspective? :D

[health_nutty]

^

How is it from a cognitive perspective? :D

Too early to tell.

[ScienceGuy]

I hope you guys can benefit from my posts.

I have benefited from many other posts on this forum, I hope to be able to contribute, to the best extent that I can possibly do so.

Are there any questions about the stack in question? I can confirm that the stack does indeed have a positive effect on both mood, energy and to some extent - memory..

Personally, I have found this thread and your posts in particular to be of great interest. You and Irish MD have brought something novel to the table with regards to your academic discussion and considerable information relating to the potential benefits and pitfalls of both D-SERINE and SARCOSINE supplementation. As such, I consider you have already contributed significantly to this forum and look forward to reading your future posts.

It seems that with regards to D-SERINE it could be an unfortunate case wherein sound theory does not translate into practice; however, it is early days yet and some further anecdotal reports would hopefully shed some light on whether or not the negatives / side effects reported by yourself and HEALTH_NUTTY are common.

The possible interaction with PIRACETAM is a very interesting point indeed. One could deduce that this might extend to the OTHER RACETAMS as well; in which case I would be most interested to hear feedback from anyone trying combining SARCOSINE with PIRACETAM or any of the OTHER RACETAMS, specifically regarding whether or not they notice the SARCOSINE in any way impacting the RACETAM's beneficial effects. UNBEATABLEKING, have you or are you willing to evaluate this and report back your findings?

[unbeatableking]

Guys. A caveat:

I find that the Racetams no longer affect me in the same way that they usually did in the past. They have lost their stimulatory properties.

This might explain why Sarcosine isn't as potent as the first time I took it.

It is apparent that Sarcosine and all of the other glycinergics have a way of inducing NMDA-receptor down regulation. A lot of anecdotes online have also pointed to this case.

There might be room for an NMDA-antagonist in this discussion. A beer or two every weekend perhaps.

It is interesting to note that NMDA-antagonists help in the reversal of amphetamine-induced NMDA receptor tolerance.

BTW, Scienceguy: I have compiled a log of sorts which I will summarize in a few minutes, one dealing with my experiences on both Sarcosine and Piracetam.

I will post it in a while. Thank you for reminding me.

[unbeatableking]

Ok, here are my experiences whilst on the Piracetam/Sarcosine combination:

A summary:

1. There really is a synergy. It has improved my memory - my visual memory quite surprisingly. The main issue is that the potency of the stack has decreased somewhat, primarily due to the downregulation of NMDA receptors as I would suppose.

2. The stack does not make me fatigued, tired or irritable.

3. There is a definite stimulatory effect, although again, this effect has waned somewhat primarily because of the reason stated above.

4. For those of you who do not take Piracetam: I have tried Sarcosine with each of the racetams at least twice (save for Oxiracetam, as I don't have any on me right now). All of them synergize with Sarcosine.

5. I take 2 gram dosages every two to three hours. The half-life falls somewhere around 2 hours. (A study has shown my evaluation to be somewhat accurate: the average clearance time of the substance is at 1.6 hours, as seen in a study done on the pharmacokinetics of Sarcosine).

[unbeatableking]

6. I have to admit however, that this enhancement is taxing. I can think, encode and recollect information better. But everything has a trade-off: Whenever I push myself too hard whilst on the stack, I get a minor headache.

[unbeatableking]

A humorous caveat: I am also taking Testforce 2 for the testosterone increasing qualities.

It has given me a terrible case of the 'runs'. Seems to have something to do with the bioavailability of DAA. Although taking the substance with a meal seems to attenuate this issue.

A humorous caveat: I am also taking Testforce 2 for the testosterone increasing qualities.

It has given me a terrible case of the 'runs'. Seems to have something to do with the bioavailability of DAA. Although taking the substance with a meal seems to attenuate this issue.

[unbeatableking]

Yes. I definitely need to re-dose Sarcosine frequently in order for it to continue to have an effect.

I'd put it around an hour and forty five minutes. For convenience, I suggest re-dosing every two hours instead. Use the 15 minutes for break time.

I am going to take an NMDA-antagonist tomorrow to see how things fare.

I feel that the substance (Sarcosine) is moderately cost-effective. It isn't dirt cheap like choline or extremely expensive like Idebenone, it is somewhere in between.

At ten dollars for 100 grams though, it seems to be a fair valuation. Let us suppose that the average person studies for 6 hours a day.

A 20 dollar supply will last the average person about a month. It seems fair.

Edited by unbeatableking, 14 September 2012 - 08:24 PM.

[health_nutty]

I'm giving 250mg of d-serine a try today. No grogginess, but I am getting irritibility (much like Piracetam does to me). I noticed this last night as well, but now I can see the effect is consistent. I'm hoping it was just the previous high doses lingering.

I'm going to take the weekend off and try 250mg again on Monday as a last ditch effort. If I get irritibility again, I'm going to ditch it.

The effects of D-serine remind me of the bad reaction I have to Piracetam: irritbility. I'm done with it.

[CIMN]

Ive been wondering if oxiracetam would combine better with sarcosine then piracetam, its like piracetam but differs slightly in structure, so any thoughts on that? maybe it would have better glycinergic synergy?

[ScienceGuy]

1. There really is a synergy. It has improved my memory - my visual memory quite surprisingly. The main issue is that the potency of the stack has decreased somewhat, primarily due to the downregulation of NMDA receptors as I would suppose.

Please can you kindly elaborate a bit about the observed SYNERGY? I am interpreting your comments that initially there is SYNERGISTIC effect between the SARCOSINE and PIRACETAM (wherein by definition the overall therapeutic effect is greater than the combination of the individual effects of the substances when taken as monotherapy) but the overall therapeutic effect then subsequently diminishes over time with repeated use... is that correct?

In which case, in your experience does the overall therapeutic effect continue to diminish more and more the longer you repeatedly administer the SARCOSINE and PIRACETAM concurrently? Or does it level out / plateau? If is does level out, does it do so above or below the comparative effect of PIRACETAM when administered as MONOTHERAPY?

My thinking is that CYCLING ON/OFF might be an option to help attain maximum SYNERGY, however this would depend on precisely what's going on and hence your answers to the above.

Edited by ScienceGuy, 15 September 2012 - 04:26 AM.

[unbeatableking]

^

Good question.


Tried it again a few hours earlier. The synergy is still there.

The experimental definition of synergy, as I experienced it, would have to be: 'an increase in processing speed and a sense of stimulation'.

I have not been on the substance long enough to evaluate a perceived tolerance in the long-run, but given my statements regarding this sense of tolerance, I would presume that the effect does indeed diminish every day I go on using the stack.

As stated, the stimulation presented by Piracetam on its own has waned somewhat.

Theoretically, an NMDA-antagonist and break time should fix the issue. I will report back later.

[unbeatableking]

I don't think the tolerance onset would be as quick for you as it was for me however.

Primarily because I am also on TestForce 2, which contains Sarcosine - a substance that I have to dose in a chronic fashion in order to continue to see androgenic gains.

I have been using it prior to sleep, so I would not worry about the substance serving as an extraneous variable within my evaluation of Sarcosine as a supplement, although without a doubt, my consumption of it would only compound the tolerance I am currently experiencing.

[metaprog]

Its been quite a while since I posted. I purchased the D-Serine from SmartPowders and tried it for 5 days with variable dosing. Suffice it to say that I was extremely disappointed. Rather than mental clarity, enhanced memory & other cognitive benefits, what I experienced was a general irritability & mild mental disorientation (inability to think clearly, a general lack of mental direction/purpose). Tried taking the recommended 1.5 grams the first day, lowered it to 1 gram the next, then half a gram, then appx. a third of a gram for the last 2 days. The aforementioned 'side-effects' were shitty enough to prompt me to stop taking it. But a friend of mine had a vastly different experience...somewhat similar to that of @UnbeatableKing.

I'll stick with DAA. Its been a phenomenal molecule for me. I've written about my experience with DAA earlier in this thread as well as in another. I usually take half the recommended dosage every other day with the full recommended dosage (which is quite potent for me - makes me feel as though I'm "under the influence" of a psychotropic) once a week. As for D-Serine, it simply isn't for me. But as mentioned earlier, my friend found it beneficial enough to purchase his own bottle. Now remains the question of how to get rid of the bottle I'm stuck with since I don't use it. Anyone interested?

[health_nutty]

I had an almost identical experience and am going to dump the bottle.

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Edited by health_nutty, 25 September 2012 - 04:24 AM.

[gizmobrain]

Aww peeps, ya'll need to learn how to trade. I would buy them off of you, but I already have a bottle that I haven't found the time to give a proper run through.

[unbeatableking]

Its been quite a while since I posted. I purchased the D-Serine from SmartPowders and tried it for 5 days with variable dosing. Suffice it to say that I was extremely disappointed. Rather than mental clarity, enhanced memory & other cognitive benefits, what I experienced was a general irritability & mild mental disorientation (inability to think clearly, a general lack of mental direction/purpose). Tried taking the recommended 1.5 grams the first day, lowered it to 1 gram the next, then half a gram, then appx. a third of a gram for the last 2 days. The aforementioned 'side-effects' were shitty enough to prompt me to stop taking it. But a friend of mine had a vastly different experience...somewhat similar to that of @UnbeatableKing.

I'll stick with DAA. Its been a phenomenal molecule for me. I've written about my experience with DAA earlier in this thread as well as in another. I usually take half the recommended dosage every other day with the full recommended dosage (which is quite potent for me - makes me feel as though I'm "under the influence" of a psychotropic) once a week. As for D-Serine, it simply isn't for me. But as mentioned earlier, my friend found it beneficial enough to purchase his own bottle. Now remains the question of how to get rid of the bottle I'm stuck with since I don't use it. Anyone interested?

What? No, I said I hated D-Serine too.

Currently using Sarcosine, which is much better. D-Serine puts me to sleep.

Why don't you just give your friend the bottle, or sell it to your friend. If he/she was genuinely interested in the product, I'm sure he/she'd be more than willing to take it off your hands.