271 replies to this topic

[metaprog]

@Unbeatable - It sounded like your experience improved after the initial sleepiness & other negative effects you mentioned, esp. when you decreased the dosage. Either way, your experience with Sarcosine is interesting. I'll look into that ASAP.

[Colli]

Well, after several days of taking Sarcosine (ranging from 500mg up to 3g), I can emphatically say that it's not for me.

In contrast to Unbeatableking's experience with Sarcosine, I have experienced fatigue, mental fogginess and a worsening of my depression. On a couple of particularly bad days, I actually considered suicide.

I think I'll leave my NMDA receptors well alone after this.

[Psionic]

looks like an antagonism is better though I still wonder about phenomenon of rapidly increased learning after ingesting nmda antagonists, looks like its serving as a reset button and brain manufacture a lots of bdnf to compensate, thanks to this (in very moderate way) I improved my piano skills in my mid 20 just after a few months of playing..

[Tubemode]

Well, after several days of taking Sarcosine (ranging from 500mg up to 3g), I can emphatically say that it's not for me.

In contrast to Unbeatableking's experience with Sarcosine, I have experienced fatigue, mental fogginess and a worsening of my depression. On a couple of particularly bad days, I actually considered suicide.

I think I'll leave my NMDA receptors well alone after this.

UK should have warned those among you suffering from depression. This is what you get for not putting up any studies - you end up leaving people in a phenomenological cloud. Either way, good anecdotes and experiences from him.

Glad you decided to dump the Sarcosine, hope you are feeling better now. As per your case, certain studies show that the antagonism of NMDA-receptors via the consumption of Ketamine can alleviate depression. Given this fact, one can theorize that one of the modes of action underlying depression as a disorder involves the agonism of NMDA-receptors.

So for those of you suffering from bipolar disorder, depression, or any of the other sub-types, I would refrain from using Sarcosine, or anything else that might have an effect on the NMDA-system.

For those who are neurologically sound on the other hand, Sarcosine might be beneficial, more so than D-Serine. Because apart from being a co-agonist at the glycine binding site, it is also a glycine transport blocker.

Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alleviation of major depressive disorder symptoms within two hours of a single, low-dose intravenous infusion of ketamine, with effects lasting up to two weeks, unlike traditional antidepressants (serotonin re-uptake inhibitors), which take weeks to reach efficacy. This delay is a major drawback to current therapies for major depressive disorder and faster-acting antidepressants are needed, particularly for suicide-risk patients. The ability of ketamine to produce rapidly acting, long-lasting antidepressant responses in depressed patients provides a unique opportunity to investigate underlying cellular mechanisms. Here we show that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor. We find that the ketamine-mediated blockade of NMDAR at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase (also called CaMKIII), resulting in reduced eEF2 phosphorylation and de-suppression of translation of brain-derived neurotrophic factor. Furthermore, we find that inhibitors of eEF2 kinase induce fast-acting behavioural antidepressant-like effects. Our findings indicate that the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast-acting antidepressants.

Edited by Tubemode, 25 September 2012 - 01:52 PM.

[Raza]

I've been playing with Sarcosine + DAA recently. Was going to go for D-Serine + DAA first, but insofar as they perform the same function, comparitive studies seemed to point at sarcosine being better - and at any rate, it is much cheaper.

From what I know about the NMDA receptor and my experience with antagonists on it, my baseline level of NMDA activation is very much on the low end. I'm scatterbrained, not very present in my environment or my body; abstract thoughts are much 'louder' in my mind than the world around me.

My experience with Sarcosine + DAA confirms this. I can't say much about memory except that I haven't experienced any obvious failings in that area while on this combo, but the improvement on focus is clearly noticable and the effects on motor function coordination in particular are profound. I practise poi, and have been for long enough that progress is very slow for me now. The difference between spinning (the practise of moving with your poi) while on or off this stack is incredible. Errors are reduced by perhaps 75% - it feels like I'd been playing with a severe handicap all that time, with movements that I knew were possible just going wrong for no discernable reason, and all of that has been lifted off me. Or like I got in a year of practise and didn't notice, or something.

Other manual tasks appear well-served, as well. The barrier between thinking about something and doing it seems thinner; while performing a task, when I think of something related to my approach to it, application now follows quickly where before I would have had to stop and think about changing what I was doing - as if the 'thinking' and 'doing' parts of my brain are communicating better. Vice versa, thinking about what I'm actually doing rather than something else entirely seems easier, too.

Edited by Raza, 25 September 2012 - 02:19 PM.

[X_Danny_X]

so now is Sarcosine the better option than D-Serine?

[Tubemode]

Seems like it.

http://www.longecity...tor-co-agonist/

[X_Danny_X]

I've been playing with Sarcosine + DAA recently. Was going to go for D-Serine + DAA first, but insofar as they perform the same function, comparitive studies seemed to point at sarcosine being better - and at any rate, it is much cheaper.

From what I know about the NMDA receptor and my experience with antagonists on it, my baseline level of NMDA activation is very much on the low end. I'm scatterbrained, not very present in my environment or my body; abstract thoughts are much 'louder' in my mind than the world around me.

My experience with Sarcosine + DAA confirms this. I can't say much about memory except that I haven't experienced any obvious failings in that area while on this combo, but the improvement on focus is clearly noticable and the effects on motor function coordination in particular are profound. I practise poi, and have been for long enough that progress is very slow for me now. The difference between spinning (the practise of moving with your poi) while on or off this stack is incredible. Errors are reduced by perhaps 75% - it feels like I'd been playing with a severe handicap all that time, with movements that I knew were possible just going wrong for no discernable reason, and all of that has been lifted off me. Or like I got in a year of practise and didn't notice, or something.

Other manual tasks appear well-served, as well. The barrier between thinking about something and doing it seems thinner; while performing a task, when I think of something related to my approach to it, application now follows quickly where before I would have had to stop and think about changing what I was doing - as if the 'thinking' and 'doing' parts of my brain are communicating better. Vice versa, thinking about what I'm actually doing rather than something else entirely seems easier, too.

What is POI? You practice it. Motor function coordination? You are doing some exercise movements or dances and the learning is coming much easier for you?

thinking about something and doing it is thinner? Are you referring to your cognitive function increasing?

[LeonardElijah]

I use Magnesium L-Threonate for the purpose of NMDA antagonism.

Also N-acetylcysteine also can help regulate NMDA activity..

Thanks. I didn't know they were selling Mag L-Threonate yet.

I'm looking for the stacks that include d-serine as well. A family member mentioned this yesterday while looking through a mail order supplements catalogue, and I didn't know what it was used for.

[Raza]

Poi is a movement/dance/performance art where you hold a cord with a weight on the end in each hand, and spin them around yourself in aesthetically pleasing patterns without getting them tangled up or hitting anything.

Here's a popular youtube film of someone spinning with fire poi.

http://www.youtube.com/watch?v=2IjdnMvBW_A

And I said the barrier between thinking about something and doing it is thinner. As in, thoughts and actions are better coordinated; there's less of a delay for a thought to be applied to action. So yes, that's one kind of cognitive function being improved.

Edited by Raza, 29 September 2012 - 10:10 PM.

[X_Danny_X]

Poi is a movement/dance/performance art where you hold a cord with a weight on the end in each hand, and spin them around yourself in aesthetically pleasing patterns without getting them tangled up or hitting anything.

Here's a popular youtube film of someone spinning with fire poi.

http://www.youtube.com/watch?v=2IjdnMvBW_A

And I said the barrier between thinking about something and doing it is thinner. As in, thoughts and actions are better coordinated; there's less of a delay for a thought to be applied to action. So yes, that's one kind of cognitive function being improved.

that is pretty good that it takes less time, assuming the thoughts are the correct ones and not the incorrect ones. my job is a little different since i have to guess and find out things. still, this will help save time.

i just wish the half life was longer, hate to always take it every 2 hours.

[BLimitless]

looks like an antagonism is better though I still wonder about phenomenon of rapidly increased learning after ingesting nmda antagonists, looks like its serving as a reset button and brain manufacture a lots of bdnf to compensate, thanks to this (in very moderate way) I improved my piano skills in my mid 20 just after a few months of playing..

Thanks to what? I have read most of the thread and I understand people are tending towards Sarcosine and D-Aspartic Acid.

What supplements are you taking? I am very interested in this increased learning ability.

[Perek]

Anyone having long-term experience of Sarcosine and or D-serine here ? A few anecdotes based on 4-5 days of taking a substance means next to nothing condsidering e.g. receptor up and down regulation.

[Thorsten3]

I'd imagine downregulation does occur. Much similar to any substance you'd use, chronically. It's best to find a few things that work for you, then work out a cycling regimen. Even that might not fully protect your brain from adapting itself though, over the long term.

Sarcosine alleviates OCD symptons, for me. But, it's half life is shite. It's annoying having to constantly redose all day. I don't notice any nootropic effect.

[Thorsten3]

For those who mentioned NMDA antagonists being superior; that isn't necessarily the case. NMDA antagonsim can provoke some nasty effects in those who are susceptible. It can induce psychotic states, that, for some (who are more vulnerable to such effects), might not be very pleasant. It all depends on your brain chemistry.

[Sunwind]

Apologies for the thread necro, but does anyone know what dosage to use of d-serine for self medication with exposure therapy? (social anxiety) I bought 100g from here http://www.smartpowd...erine-100g.html

[lourdaud]

I've been playing with Sarcosine + DAA recently. Was going to go for D-Serine + DAA first, but insofar as they perform the same function, comparitive studies seemed to point at sarcosine being better - and at any rate, it is much cheaper.

From what I know about the NMDA receptor and my experience with antagonists on it, my baseline level of NMDA activation is very much on the low end. I'm scatterbrained, not very present in my environment or my body; abstract thoughts are much 'louder' in my mind than the world around me.

My experience with Sarcosine + DAA confirms this. I can't say much about memory except that I haven't experienced any obvious failings in that area while on this combo, but the improvement on focus is clearly noticable and the effects on motor function coordination in particular are profound. I practise poi, and have been for long enough that progress is very slow for me now. The difference between spinning (the practise of moving with your poi) while on or off this stack is incredible. Errors are reduced by perhaps 75% - it feels like I'd been playing with a severe handicap all that time, with movements that I knew were possible just going wrong for no discernable reason, and all of that has been lifted off me. Or like I got in a year of practise and didn't notice, or something.

Other manual tasks appear well-served, as well. The barrier between thinking about something and doing it seems thinner; while performing a task, when I think of something related to my approach to it, application now follows quickly where before I would have had to stop and think about changing what I was doing - as if the 'thinking' and 'doing' parts of my brain are communicating better. Vice versa, thinking about what I'm actually doing rather than something else entirely seems easier, too.

Hi man,

I found this old post of yours quite interesting. Did you stick with DAA and sarcosine and at what doses were/are you on?
I'm asking since I seem to suffer from low NMDA expression (horrible fine motor skills, difficulties with abstractive thought etc) and I had a tremendous experience one time when I tried DAA, piracetam and cannabis where I felt very much in touch with my body and had a drastically enhanced sense of orientation. Unfortunately I experienced some tingling in the back of my head and started to worry about excitoxity so I never dried it again.
You have any idea if DAA should be safe or not, in, or not in, combination with racetams and other glutaminergic potentiators?

/lourdaud

[lourdaud]

I've been playing with Sarcosine + DAA recently. Was going to go for D-Serine + DAA first, but insofar as they perform the same function, comparitive studies seemed to point at sarcosine being better - and at any rate, it is much cheaper.

From what I know about the NMDA receptor and my experience with antagonists on it, my baseline level of NMDA activation is very much on the low end. I'm scatterbrained, not very present in my environment or my body; abstract thoughts are much 'louder' in my mind than the world around me.

My experience with Sarcosine + DAA confirms this. I can't say much about memory except that I haven't experienced any obvious failings in that area while on this combo, but the improvement on focus is clearly noticable and the effects on motor function coordination in particular are profound. I practise poi, and have been for long enough that progress is very slow for me now. The difference between spinning (the practise of moving with your poi) while on or off this stack is incredible. Errors are reduced by perhaps 75% - it feels like I'd been playing with a severe handicap all that time, with movements that I knew were possible just going wrong for no discernable reason, and all of that has been lifted off me. Or like I got in a year of practise and didn't notice, or something.

Other manual tasks appear well-served, as well. The barrier between thinking about something and doing it seems thinner; while performing a task, when I think of something related to my approach to it, application now follows quickly where before I would have had to stop and think about changing what I was doing - as if the 'thinking' and 'doing' parts of my brain are communicating better. Vice versa, thinking about what I'm actually doing rather than something else entirely seems easier, too.

Hi man,

I found this old post of yours quite interesting. Did you stick with DAA and sarcosine and at what doses were/are you on?
I'm asking since I seem to suffer from low NMDA expression (horrible fine motor skills, difficulties with abstractive thought etc) and I had a tremendous experience one time when I tried DAA, piracetam and cannabis where I felt very much in touch with my body and had a drastically enhanced sense of orientation. Unfortunately I experienced some tingling in the back of my head and started to worry about excitoxity so I never dried it again.
You have any idea if DAA should be safe or not, in, or not in, combination with racetams and other glutaminergic potentiators?

/lourdaud

What the hell, I did it again - that was meant to be a private message. I'll stop zolpidem as soon as finals are over...

[aprkak]

What about bioscience nutraceuticals? Just ordered 100g Sarcosine for $25 ($10 shipping tho) - hoping their product is good qlty. Looking for help with severe OCD (unrelenting obsessive anxiety). If it goes well, will maybe order from them again or possibly smart powders if reputation is better/worth it.

[Godof Smallthings]

Bioscience Nutraceuticals is the same company as Cerebral Health.

http://www.reddit.co...nutraceuticals/

http://www.reddit.co...esults_warning/

I would not order from them after these incidents. Especially the later one is very serious.

[protoject]

There's a company called Health Sources who I've bought D-Serine and Sarcosine from. I did not test their batches at all but it seems legit. A crystalline sugary substance that indeed tastes like sugar. Sarcosine seems to hydrolyze after a while and produce somewhat of a fishy scent (Ive had it for about 2 years)/// theyre from China. Depending on what agent you speak with or if you've ordered from them before they might want you to order a business amount. i.e. 1 kg rather than 200 g.

[normalizing]

im just curious, any long term reports on usage of l-serine or d-serine ? so far, a lot of discussion on sarcosine and also people seeiking sources to buy it instead of people actually discussing experiences with them.

[Ames]

http://jpet.aspetjou.../311/2/836.long

[normalizing]

^ so would it even work to begin with if you supplement with d-serine enough to cause excitotoxicity? from what i understand, d-serine is not something to fuck with. but there are tons of other articles showing supplementing actually causes benefit regard schizophrenia for one. not sure what to make of this. you should at least give your opinion :/

[Ames]

In addition to the above linked-to article, I have before read other articles that have led me to believe that D-Serine is too potentially neurotoxic to mess around with. If I can dig out some more I will.

According to my understanding on the matter, whenever we attempt to agonize NMDA receptors we run the risk of neurotoxicity. Conversely, too much NMDA antagonism also causes problems (Olney's Lesions). The trick lies in striking a balance between effectiveness and minimal dose. Going on the research that I remember reading, I think that the maximum dose before neurotoxicity occurs is much lower for D-Serine than almost any other NMDA agonist. Only glutamate itself would likely compete, and I'm not sure that D-Serine isn't worse. I'm also not sure why you would forgo trying the much weaker, more benign L-Serine first if you wished to try a serine isomer.

Before D-Serine, you would want to try Sarcosine, TMG, or DMG. Going straight to D-Serine for nootropic purposes is sort of like going straight to D-Methamphetamine for ADD. Sarcosine is well known to help in schizophrenia, and from the reports that I have read most schizophrenics get a much better response from Sarcosine because of the markedly reduced negative side effects compared with D-Serine. I think that you could reach your desired level of benefit with one of the aforementioned molecules while maintaining a much higher margin of error buffer before significant neurotoxicity is realized. In fact, Sarcosine and TMG (and likely DMG but I haven't confirmed) both provide excitotoxicity protection within a certain dose range. I haven't seen any such reasearch that D-Serine confers any such protection. The only related research is about its ability to facilitate neurotoxicity.

Edited by golgi1, 09 August 2014 - 10:18 PM.

[thises]

In addition to the above linked-to article, I have before read other articles that have led me to believe that D-Serine is too potentially neurotoxic to mess around with. If I can dig out some more I will.

According to my understanding on the matter, whenever we attempt to agonize NMDA receptors we run the risk of neurotoxicity. Conversely, too much NMDA antagonism also causes problems (Olney's Lesions). The trick lies in striking a balance between effectiveness and minimal dose. Going on the research that I remember reading, I think that the maximum dose before neurotoxicity occurs is much lower for D-Serine than almost any other NMDA agonist. Only glutamate itself would likely compete, and I'm not sure that D-Serine isn't worse. I'm also not sure why you would forgo trying the much weaker, more benign L-Serine first if you wished to try a serine isomer.

Before D-Serine, you would want to try Sarcosine, TMG, or DMG. Going straight to D-Serine for nootropic purposes is sort of like going straight to D-Methamphetamine for ADD. Sarcosine is well known to help in schizophrenia, and from the reports that I have read most schizophrenics get a much better response from Sarcosine because of the markedly reduced negative side effects compared with D-Serine. I think that you could reach your desired level of benefit with one of the aforementioned molecules while maintaining a much higher margin of error buffer before significant neurotoxicity is realized. In fact, Sarcosine and TMG (and likely DMG but I haven't confirmed) both provide excitotoxicity protection within a certain dose range. I haven't seen any such reasearch that D-Serine confers any such protection. The only related research is about its ability to facilitate neurotoxicity.

 

Yeah would love to see that article

[Ames]

Yeah would love to see that article

Would love to see what article? I posted the article to which I was referring. If you mean other articles that document the potential neurotoxicity of D-Serine, then go to google scholar, begin searching (the articles are there in abundance) and then make your own informed decision.

Remember, my post only highlights my perspective and resulting decision on D-Serine. You have to satisfy yourself and make your own risk/reward based decision. That D-Serine, or evenly something as relatively benign as glycine, can be neurotoxic isn't in question. It's about dose, reward, and risk tolerance. My perspective is that there are molecules that are likely safer, per equivalent dose, than D-Serine and that their comparative lack of side effects will even make them seem more effective although they may have weaker action at the NMDA site and associated receptors. A major complaint of schizophrenics, when it comes to D-Serine, is that it makes them feel sleepy and out of it whereas Sarcosine tends to produce the desirable effect more reliably. Their perceived negative D-Serine experiences are likely a result of quickly exceeding thresholds for a neurotoxic reaction.

My point is that you should do your own research. I can only relate my perception based on my research. Though, there is also no harm in first trying less potent compounds.

[Ames]

Here's a study that compared D-Serine and Sarcosine in schizophrenia treatment. Sarcosine was found to be more effective:

http://www.rima.org/...05_1196-204.pdf

Also, here's a study on sarcosine preconditioning that found that such preconditioning leads to protection against ischemia in the hippocampus through reduction in glutamate release during ischemic insult. Note that the beneficial response was dependent on a dose of 100mg/kg. A 30mg/kg dose provided no neuroprotection and the 300 mg/kg dose results were close to the negative control:

http://www.researchg...4f5b3066c000000

Also, I suggest that anyone who is interested in comparing D-Serine to TMG or Sarcosine got to google scholar and search the following terms; (note: "Betaine" in the common term used for Trimethylglycine [TMG] - not to be confused with Betaine HCL):

D-Serine + neurotoxic
D-Serine + hippocampus
D-Serine + neuron
D-Serine + excitotoxicity

Now switch "Betaine" and, in different searches, "Sarcosine" out for "D-Serine". You'll find some interesting papers. Additional 'bonus' terms to search for, that include research around these molecules, are: "memory", "alzheimer's", and "stroke". I'm on an ipad, otherwise I'd post some more links.

Edited by golgi1, 10 August 2014 - 03:13 PM.

[Ames]

Another facet to all of the molecules that we've been discussing, that you want to be aware of, is that their correlation to cancer is apparently in dispute (for some) but that correlation exists. I'll start you off with a few studies, some apparently conflicting, but you'll have to do your own research to reach your own conclusion about probable safety and risk:

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

http://onlinelibrary....28347/abstract

Choline intake and risk of lethal prostate cancer: incidence and survival

http://www.ncbi.nlm....?report=classic

Serine, but Not Glycine, Supports One-Carbon Metabolism and Proliferation of Cancer Cells

http://www.cell.com/...1247(14)00347-7

Serine, glycine and the one-carbon cycle: cancer metabolism in full circle

http://www.ncbi.nlm....les/PMC3806315/

Progression of Prostate Carcinogenesis and Dietary Methyl Donors: Temporal Dependence

http://cancerprevent.../2/229.abstract

Choline and Betaine Intake and the Risk of Colorectal Cancer in Men

http://cebp.aacrjour...t/19/3/884.full

The Role of Sarcosine Metabolism in Prostate Cancer Progression

http://www.ncbi.nlm....les/PMC3638352/

 

Cancer Risk: Propsective Investigation of Seven Circulating B Vitamions and Metabolites

 

http://cebp.aacrjour.../18/5/1538.full

 

Sarcosine in Urine after Digital Rectal Examination Fails as a Marker in Prostate Cancer Detection and Identification of

Aggressive Tumours

 

http://www.urosource...entzmik_AIP.pdf

 

Plasma sarcosine does not distinguish early and advanced stages of prostate cancer

 

http://www.scielo.or...ipt=sci_arttext

 

Choline and betaine intake and the risk of colorectal cancer in men

 

http://www.ncbi.nlm....les/PMC2882060/

 

Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation

 

http://www.ncbi.nlm....les/PMC3526189/

 

Cytotoxic Effect of the Red Beetroot (Beta vulgaris L.) Extract Compared to Doxorubicin (Adriamycin) in the Human Prostate (PC-3) and Breast (MCF-7) Cancer Cell Lines

 

http://www.ingentaco...000003/art00007

 

Serum Methionine Metabolites Are Risk Factors for Metastatic Prostate Cancer Progression

 

http://www.plosone.o...al.pone.0022486

 

Methionine restriction induces apoptosis of prostate cancer cells via the c-Jun N-terminal kinase-mediated signaling pathway

 

http://www.sciencedi...304383501008527

 

Dietary intake of B vitamins and methionine and prostate cancer incidence and mortality

 

http://link.springer...0552-012-9954-5

 

Choline and Betaine in Health and Disease (Research Review)

 

http://www.folk.uib....1_jimd_34_3.pdf

 

 

 

Edited by golgi1, 10 August 2014 - 04:36 PM.

[Ames]

Last, two more studies (one is a 12 subject study for a Master's Thesis) that, instead of focusing on cancer, provides evidence for an anabolic hormonal response to Betaine in men:

 

The Effect of Betaine Supplementation on Performance and Muscle Mechanisms

 

http://digitalcommon...cle mechanisms"

 

and

 

Effect of betaine supplementation on power performance and fatigue

 

http://www.jissn.com/content/6/1/7

Edited by golgi1, 10 August 2014 - 04:47 PM.