52 replies to this topic

[Daniel Cooper]

Looking for supplements that lower the production of glutamate in the brain. 

 

Any ideas?

 

 

 

[iseethelight]

B12, zinc, magnesium  all lower glutamate via nmda antagonism, etc. 

[BlueCloud]

Funny, I was researching the subject just this morning.

 

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues. It does however come with its own set of problems, but mainly at high doses and if used long-term ( cardiac issues due to renal nitrite inhibition https://www.ncbi.nlm...bmed/25499330      )

It's something I'm going to try soon and will report.

 

Also, neural inflammation releases glutamate. So anything that reduces inflammation should be good too.

[Daniel Cooper]

B12, zinc, magnesium  all lower glutamate via nmda antagonism, etc. 

 

I've seen discussions of B12, magnesium, and zinc lowering glutamate, but I've never seen any studies quoted to back that up.  They may be out there, but I did not find them.

[Daniel Cooper]

Funny, I was researching the subject just this morning.

 

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues. It does however come with its own set of problems, but mainly at high doses and if used long-term ( cardiac issues due to renal nitrite inhibition https://www.ncbi.nlm...bmed/25499330      )

It's something I'm going to try soon and will report.

 

Also, neural inflammation releases glutamate. So anything that reduces inflammation should be good too.

 

I see this study supports the position - https://www.ncbi.nlm...pubmed/19581567

 

Also, that link in your post above appears to be broken.

 

 

What sort of dose of NAC are you contemplating?

Edited by Daniel Cooper, 27 January 2018 - 01:22 PM.

[BlueCloud]

 

Funny, I was researching the subject just this morning.

 

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues. It does however come with its own set of problems, but mainly at high doses and if used long-term ( cardiac issues due to renal nitrite inhibition https://www.ncbi.nlm...bmed/25499330      )

It's something I'm going to try soon and will report.

 

Also, neural inflammation releases glutamate. So anything that reduces inflammation should be good too.

 

I see this study supports the position - https://www.ncbi.nlm...pubmed/19581567

 

Also, that link in your post above appears to be broken.

 

 

What sort of dose of NAC are you contemplating?

 

 

the good link https://www.ncbi.nlm...pubmed/25499330

But I can't find anymore where I read the full abstract ( the link above doesn't have it )

 

Dosage : I'll start at 600mg, and work my way up if nothing is happening..

[Believer]

Manganese (increases conversion of glutamate to glutamine)

Creatine (works on glutamate transporters, is so effective that it causes flat affect)

Nicotinamide (not sure about its mechanism of action but it clearly has effects)

Vitamin K2 (mild effect on lowering glutamate, mostly lowers calcium which glutamate needs to do its things)

Fasting (not a supplement, I know)

 

Stay away from junk like acetylcysteine which is a glutamate agonist and takes months to even mildly lower glutamate levels. Theanine is junk, too, for lowering glutamate as it can convert to glutamate.

Taurine and some of the other junk simply does not work.

[Believer]

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues.

Absolutely wrong. Actually look at the studies. I don't understand how you could claim this total nonsense.

Vitamin K2 works better than NAC. NAC takes MONTHS to even mildly reduce glutamate levels. And it is NOT a glutamate antagonist. Look at its pharmacology, it stimulates metabotropic and ionotropic glutamate receptors. It's a glutamate agonist.

 

NAC activates the mGluR5 receptor (in larger dosages) which is what CAUSES glutamate-induced OCD and autistic rage (glutamate rage). It does absolutely nothing to antagonize this receptor in anyway, at any dosage.

And the receptor does not downregulate either, as you will quickly find out.

 

It's recommended for autism based upon the most stupid reasons just as inositol, a serotonin agonist, is recommended for treating symptoms of excessive activity of serotonin. It doesn't get any more unintelligent than this. At least inositol has the ability to actually work if you take large enough dosages.

 

[Nate-2004]

Berberine in low doses: i.e. 300-400 mg 3 times per day. 

 

NAC may also have some effect in combination as mentioned above. Glutamate is a current research focus with essential tremor and I'm constantly looking for ways to mitigate it.

[Daniel Cooper]

 

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues.

Absolutely wrong. Actually look at the studies. I don't understand how you could claim this total nonsense.

Vitamin K2 works better than NAC. NAC takes MONTHS to even mildly reduce glutamate levels. And it is NOT a glutamate antagonist. Look at its pharmacology, it stimulates metabotropic and ionotropic glutamate receptors. It's a glutamate agonist.

 

NAC activates the mGluR5 receptor (in larger dosages) which is what CAUSES glutamate-induced OCD and autistic rage (glutamate rage). It does absolutely nothing to antagonize this receptor in anyway, at any dosage.

And the receptor does not downregulate either, as you will quickly find out.

 

It's recommended for autism based upon the most stupid reasons just as inositol, a serotonin agonist, is recommended for treating symptoms of excessive activity of serotonin. It doesn't get any more unintelligent than this. At least inositol has the ability to actually work if you take large enough dosages.

 

I don't know Believer, there is some evidence that NAC operates on the glutamatic system.  I've never seen anyone claim it is an agonist.  I've seen claims variously that it is an antagonist or actually down regulates the production of glutamate.  Frankly, I'd rather it acted to reduce glutamate production rather as an antagonist as I'd fear receptor upregulation with any sort of long term use.

 

Here's some studies:

 

https://www.ncbi.nlm...les/PMC3044191/

 

https://www.ncbi.nlm...pubmed/19581567

 

https://www.ncbi.nlm...pubmed/27007062

 

 

From that first paper:

 

Effects on neurotransmission

 

  Glutamate

 

In addition to the effects on oxidative balance, alterations in cysteine levels have also been shown to modulate neuro-transmitter pathways, including glutamate and dopamine (DA; Fig. 1).23,24 Cysteine assists in the regulation of neuronal intra- and extracellular exchange of glutamate through the cystine–glutamate antiporter. Whereas this antiporter is ubiquitous throughout all cell types, in the brain it is preferentially located on glial cells.25 The dimer, cystine, is taken up by astrocytes and exchanged for glutamate, which is released into the extracellular space. This free glutamate appears to stimulate inhibitory metabotropic glutamate receptors on glutamatergic nerve terminals and thereby reduce the synaptic release of glutamate.26 Given that relation, the amount of cysteine in the system as well as the feedback via GSH production by neurons may directly regulate the amount of glutamate present in the extracellular space. Furthermore, GSH itself has been shown to potentiate brain N-methyl-d-aspartate receptor response to glutamate in rats.27,28 Changes in the levels of neuronal GSH may not only alter available glutamate levels, but also have direct consequences on glutamatergic function.

 

 

Dopamine

 

In addition to modulating glutamate levels through the cystine–glutamate antiporter, NAC has also been shown to alter DA release. Following amphetamine treatment to rat striatal slices, NAC has been shown to facilitate vesicular DA release at low doses in striatal neurons and inhibit release at millimolar concentrations.29 In monkeys, NAC has been shown to protect against reductions in DA transporter levels following repeated methamphetamine administration,30 suggesting one mechanism whereby increased DA release was facilitated in the previous study. Glutathione has also been shown to increase glutamate agonist–evoked DA release in mouse striatal neurons.23

 

[Daniel Cooper]

Berberine in low doses: i.e. 300-400 mg 3 times per day. 

 

NAC may also have some effect in combination as mentioned above. Glutamate is a current research focus with essential tremor and I'm constantly looking for ways to mitigate it.

 

 

Nate -

 

If you haven't looked you might also give ginkgo a study.

 

It seems to either downregulate glutamate production or act as an antagonist.  

 

The only issue I see with it for your use is that is also is a NAM of GABA receptors, which may not be desirable in your application.

[Believer]

It's funny how people attack others for trying to help. I expect better from people on Reddit and they're pretty terrible.

As for NAC, quoting from Wikipedia,

https://en.wikipedia...harmacodynamics

"L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR_2/3 receptors, and at higher doses of acetylcysteine, mGluR₅.^[67][68]"

 

^{The Wikipedia article was edited and force contained better wording. But NAC increases glutamate activity and exacerbates symptoms of autism, for example.}

[Daniel Cooper]

It's funny how people attack others for trying to help. I expect better from people on Reddit and they're pretty terrible.

As for NAC, quoting from Wikipedia,

https://en.wikipedia...harmacodynamics

"L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR_2/3 receptors, and at higher doses of acetylcysteine, mGluR₅.^[67][68]"

 

^{The Wikipedia article was edited and force contained better wording. But NAC increases glutamate activity and exacerbates symptoms of autism, for example.}

 

 

About the part in bold - that first paper also cites this effect, but they detail a mechanism whereby release of glutamate into the extracellular space results in an overall downregulation of glutamate production.  It's actually in the part I quoted above.

[Believer]

I have taken NAC daily for a long time. As I said earlier, no such downregulation occurs. The effects of overactivity of glutamate (which seems to show itself in mGluR5 activation, 5ht2a activation with serotonin) does not even in the slightest lessen.

Sometimes studies are dead wrong and this is one example.

[Daniel Cooper]

I have taken NAC daily for a long time. As I said earlier, no such downregulation occurs. The effects of overactivity of glutamate (which seems to show itself in mGluR5 activation, 5ht2a activation with serotonin) does not even in the slightest lessen.

Sometimes studies are dead wrong and this is one example.

 

I guess I'll find out. I'm going to trial 1200mg/day.  Looks like it can take up to 2 months to work if it works at all.

[normalizing]

Funny, I was researching the subject just this morning.

 

N.A.C is the best thing we have. N-Acetylcysteine antagonizes glutamate. There's research showing its efficacy in OCD and various psych issues. It does however come with its own set of problems, but mainly at high doses and if used long-term ( cardiac issues due to renal nitrite inhibition https://www.ncbi.nlm...bmed/25499330      )

It's something I'm going to try soon and will report.

 

Also, neural inflammation releases glutamate. So anything that reduces inflammation should be good too.

 

that cant be all bad, just take heart supportive stuff with it then, like taurine and fish oil

 

but since someone said taurine can be useless to lower glutamate, how about campral, which is more bioavailable form of taurine? what you think about that one?

Edited by hazy, 01 February 2018 - 04:58 AM.

[kurdishfella]

huperzine a

[Daniel Cooper]

huperzine a

 

 

I'm unclear on whether hurperzine is either a glutamate receptor antagonist/glutamate downregulator or whether it protects the brain from glutamate excitotoxicity.  It seems to be the latter, which is certainly important, but if that's the case I suspect you're still going to feel the effects of excessive glutamate even if the damage will be to some extent mitigated.

 

I'd love for someone to correct me if I'm wrong about that.

Edited by Daniel Cooper, 01 February 2018 - 10:26 PM.

[normalizing]

the best way to know which works is when you binge drink and try to stop you get that excitotoxic state that i have experienced it many times but only way i fixed it is with more alcohol or sedatives. but i think its good idea to trial some of the mentioned substances on this to see if they work. as far as i know, huperzine a for one didnt help

Edited by hazy, 02 February 2018 - 01:13 AM.

[Galaxyshock]

Curcumin seems to have both glutamate release blocking and receptor expression decreasing effects.

[Daniel Cooper]

Curcumin seems to have both glutamate release blocking and receptor expression decreasing effects.

 

Thanks.  I'll look into that.

[Believer]

I'll make a correction regarding vitamin K. The gelatin capsule probably contains glutamate but if we ignore this I think sufficiently high dosages of vitamin K lowers glutamate by using glutamate as a cofactor.

However, vitamin K in lower dosages may also slightly elevate glutamate at random times because glutamate, which is used as a cofactor, is recycled or whatever it is.

[Ames]

Taurine and some of the other junk simply does not work.

 

I've been dealing with neurological inflammation for about 19 years. Taurine and Excedrin are the only substances that I've found to reliably prevent / reduce it.

 

Taurine works best as a prophylactic taken consistently every day in either pill form (500 mg) or in an energy drink. Expect a noticeable persistent reduction in the negative symptoms of glutamate overload in 1-2 weeks.

 

Though, it will reduce inflammation to an extent and works especially well to enhance the abortive (Excedrin). Its just not usually adequate for an abortive on its own, for all but mild inflammation.

 

One 500 mg Taurine pill and one Excedrin is my go-to for everything but the most painful headache. For that, I take two Excedrin.

 

Taurine works so well that I will notice a small measure of cognitive impairment at 1000 mg (temporary word retrieval and grogginess). So, I stick to a 500 mg dose that is almost side-effect free.

 

I used to take lithium orotate, which had similar effects, but Taurine is cleaner with less side effects (Lithium being stronger, however, at 2% of the dose - but hard on the kidneys and too inhibitory for long term use imo).

 

In fact, side effects are the lowest for Taurine of anything that I've ever taken aside from simple vitamins. The most I notice is a slight constrictive effect that I really only feel (the next morning) if I take it too late at night. And it is mild and tends to only come after several days of using it like that. Skipping a couple days will quickly reverse any (usually small) measure of acclimation to it after taking it for a while. 

 

Its also the best sleep aid I've ever found, for its overall smoothness and enhancement (instead of reduction of) sleep quality. I've turned family members onto it for this use. I will take it to cure 3 am insomnia (which I rarely get anymore) or to calm my brain or if it is too alert when I hit the pillow, but the best effect is if you can think to take it at least one hour before bed. 

 

It will also reduce fatigue if you wake up without enough sleep, but enough to not absolutely need to go back to bed. If you need more sleep, it it will help you drop back to sleep. As I stated, its the single best sleep aid and that extends to reducing the symptoms of less sleep even without going back to bed. 

 

In sum, I'm a big fan and I hold that Taurine shouldn't be dismissed: at least as an adjunct supplement for people with inflammation / glutamate issues. 

Edited by golgi1, 18 August 2018 - 07:10 AM.

[Ames]

Absolutely wrong. Actually look at the studies. I don't understand how you could claim this total nonsense.

Vitamin K2 works better than NAC. NAC takes MONTHS to even mildly reduce glutamate levels. And it is NOT a glutamate antagonist. Look at its pharmacology, it stimulates metabotropic and ionotropic glutamate receptors. It's a glutamate agonist.

 

I've never felt anything remotely beneficial from NAC, having to do with glutamate / inflammation nor anything else.

 

In fact, I reliably and very noticeably get the cardio-pulmonary pressure symptom that he studies warn about. Its the single scariest supplement that I've ever taken, for that reason. 

Edited by golgi1, 18 August 2018 - 07:04 AM.

[resveratrol_guy]

Over the years I've noticed that consumption of foods rich in glutamic acid (e.g. almonds) leads to tinnitus and sleep disruption. Since zero intake is probably unsafe, and since it's in so many foods, my only choice has been to mitigate those disruptive effects. I haven't tried taurine, but zinc gluconate (50 mg/d), cat's claw (1 pill daily as needed), and grapefruit juice seem to be most effective. The zinc connection is obvious, considering its role in synaptic modulation. Cat's claw's mechanism of action is less clear, and by the way it can temporarily inhibit my visual memory when I take it daily. Grapefruit juice is a total mystery to me, but it does something to quell tinnitus, and thus presumably glutamate excitotoxicity. (Just be careful due to its dose-enhancing effect on a wide range of other compounds.) I've made these discoveries by process of elimination, but of course this is an N=1 study, so take it as a hint and nothing more.

 

Edited by resveratrol_guy, 18 August 2018 - 05:56 PM.

[normalizing]

golgi1, have you looked into TUDCA which is more absorbable and more studied form of taurine? i think you should look into and try it and see if helps even more. im curious too as ive read much more about it as studies goes than plain taurine.

[Hip]

See Five ways to reduce your ME/CFS "wired but tired" hyperaroused brain state for ideas on how to reduce brain extracellular glutamate and reduce NMDA receptor activation by glutamate.

[Gallus]

I think most people talk about 'lowering glutamate' but in reality they likely have excess Quinolinic acid circulating, which is a potent NMDA Agonist, as a result of the Kynurenine pathway of Tryptophan metabolism...  This seems particularly true when there is 'Chronic inflammation' caused by stress, infection or other medical issues (chronic inflammation being the blanket term but specifically IDO production increased by INF-ɣ and TNF-α).  Incidentally the same pathway reduces the amount of serotonin in the brain, so it is a double-edged sword...  

 

Summarized here (if overly simplified) https://www.youtube....h?v=QeKCp_F9VLI

 

https://www.research..._fig1_279733839

 

 

[gamesguru]

Curcumin seems to have both glutamate release blocking and receptor expression decreasing effects.

 

where does he get this stuff, it's like he's a frickin genius or something

 

as for the other suggestions

taurine i would be leery of, GABAergic deficits lurk around every corner

magnesium i can vouch for

 

to add some new suggestions of my own to this thread: bacopa, apigenin, quercetin, baicalein, luteolin, low glutamine diet, (get ready for some obscure and cryptic ones) bromocriptine, riluzole, H3 agonists, THC, and not CBD or lithium

[nickdino]

Hi, everyone. Is there a better form or combination of NAC available anywhere? I've read that NAC has poor bioavailability.

Experiments with NAC Amide have been done with positive outcomes but i don't think its available and i've seen a yt video that mentions a combo of NAC and S Acetyl Glutathione.