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Any supplements that lower the production of glutamate?

glutamate

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#31 DeltaWave

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Posted 05 November 2018 - 07:19 PM

glutamate is essential for learning and memory

have too much glutamate? go study!

 

https://www.scienced...124081390000043


Edited by DeltaWave, 05 November 2018 - 07:21 PM.


#32 gamesguru

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Posted 05 November 2018 - 08:08 PM

if you have too much glutamate you probably have schizophrenic symptoms and can't study very effectively.  Better to go outside and get some exposure to green light or natural vibes or some pseudo-BS like that


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#33 Daniel Cooper

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Posted 05 November 2018 - 08:38 PM

glutamate is essential for learning and memory

have too much glutamate? go study!

 

https://www.scienced...124081390000043

 

Glutamate is essential for learning and memory, but it does not follow that studying will lower glutamate in any meaningful way.



#34 John250

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Posted 06 November 2018 - 01:26 AM

if you have too much glutamate you probably have schizophrenic symptoms and can't study very effectively. Better to go outside and get some exposure to green light or natural vibes or some pseudo-BS like that


Don’t most nootropics and amphetamines increase glutamate and the main benefit from them is focus? For example noopept is known for its cognitive enhancement and I believe it increases glutamate a lot. But I’assume the proper balance between dopamine, glutamate and other neurotransmitters have to be in the correct ratio to maximize cognition.
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#35 gamesguru

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Posted 07 November 2018 - 03:16 AM

glutamate where. locations matters you know.



#36 Hip

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Posted 07 November 2018 - 03:22 AM

See: Five ways to reduce your ME/CFS "wired but tired" hyperaroused brain state



#37 Phoebus

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Posted 07 November 2018 - 05:23 AM

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

 

 

okay great, so how does one go about lowering Quinolinic acid?



#38 gamesguru

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Posted 07 November 2018 - 01:35 PM

also doesn't explain why turmeric and magnesium consistently help take the edge off pro-glutamate things, like tea and ginseng

 

if you just go raising glutamate and you do it for months and months, you will have your regrets :sleep:



#39 Gallus

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Posted 07 November 2018 - 07:20 PM

okay great, so how does one go about lowering Quinolinic acid?

 

Kynurenine Pathway

To reduce Quinolinic acid production (thereby reducing NMDA receptor antagonism, Anxiety, Depression etc), by diverting Tryptophan toward Serotonin production at the top of the pathway you would want to inhibit the Enzymes that convert Tryptophan into Kynurenine.  The enzymes responsible are IDO1, IDO2 and TDO.  TDO is restricted to the liver but IDO is also active in the brain so preferable to target.

 

The simplest way to do this may be to restrict any consumption of dietary Tryptophan only alongside an IDO inhibitor.  Pharma are working on harnessing this as a drug target, but there are natural food sources such as Rosmarinic acid (found in Rosemary) and Circumin (Found in Turmeric) which are effective IDO inhibitors but have a short half-life (hence some dietary restriction needed to make effective)..

 

An example of a workable way to test this is to eat a healthy balanced diet (just to ensure all other cofactors are present) ... but with a few rules:

 

Here's The Gallus Method : )

 

1)  Restrict eating to an 8 hour window - I usually have lunch around 12pm and dinner around 7pm.. snacks etc in between fine.

2)  No rules for drinks, unless they containt Tryptophan, like Milk (if so restrict to the 8 hour window)

3)  Include Tryptophan rich foods in your meals if you can... meat, fish are the go-to's

4)  (The important bit)... Take IDO inhibitor supps with lunch at 12, then again with dinner... I take 1x500mg Rosemary extract (look for Rosmarinic acid content on label) and about 500mg Turmeric with each meal...

DISCLAIMER - would think it's completely safe as normal dietary do your own checks etc


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#40 gamesguru

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Posted 07 November 2018 - 10:44 PM

what does not eating 16 hours out of the day accomplish?  and a high tryptophan diet is probably also high tyrosine and high glutamine, which may not be ideal for everyone.



#41 Gallus

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Posted 07 November 2018 - 11:20 PM

what does not eating 16 hours out of the day accomplish?  and a high tryptophan diet is probably also high tyrosine and high glutamine, which may not be ideal for everyone.

 

"what does not eating 16 hours out of the day accomplish?"   -  The theory here is it's just easier to control and synchronize Tryptophan intake with IDO inhibition ..  e.g. if you're eating throughout the whole day you'd probably need to supplement constantly with IDO inhibitors, or you could eat anytime but would need to check Tryptophan content of everything...

 

"a high tryptophan diet is probably also high tyrosine and high glutamine, which may not be ideal for everyone." -   This is true .. although not really talking about anything too  extreme here, example chicken salad for lunch, salmon & veg for dinner etc etc ,, just a normal healthy diet.



#42 gamesguru

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Posted 07 November 2018 - 11:35 PM

honestly i like your ideas here, they are well-intentioned and original.  the implementation is just poor; curcumin is probaly not the most potent and rosmarinic acid has its drawbacks.  and while someone detoxing alcohol or something might benefit from the protocol, the average individual just isn't full to the brim with toxins, environmental or otherwise.  if anything they're deficient in key nutrients, magnesium, selenium, potassium and vitamin E, and they have too much "junk" too much protein.  trying to cram all their food in 8 hours is unlikely to help with that


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#43 Hip

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Posted 08 November 2018 - 12:03 AM

doesn't explain why turmeric and magnesium consistently help take the edge off pro-glutamate things

 

 

Magnesium is high doses (which can only be obtained from injection or transdermal magnesium cream) is a good NMDA receptor blocker, so this inhibits the effects of high extracellular glutamate on the NMDA receptor.

 

 

 

Turmeric reduces brain inflammation (neuroinflammation), and neuroinflammation produces copious quantities of glutamate. See this paper:

Activated microglia are also known to secrete a large amount of glutamate via their glutamate transporters,

 

And this paper:

When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation.

 

And this paper:

Our findings suggest that activated microglia trigger the elevation of extracellular L-Glu through their own release of L-Glu, and astrocyte L-Glu transporters are downregulated as a result of the elevation of astrocytic intracellular L-Glu levels, causing a further increase of extracellular L-Glu. Our data suggest the new hypothesis that activated microglia collude with astrocytes to cause the elevation of extracellular L-Glu in the early stages of neuroinflammation.

 

Thus any drugs or supplements like turmeric that can reduce neuroinflammation and thus microglial activation may reduce brain extracellular glutamate levels. 

 

 

 

When I had moderate to severe generalized anxiety disorder triggered by a viral infection of my brain, I developed a hypothesis that the anxiety symptoms were due to excess extracellular glutamate caused by chronic neuroinflammation from the viral infection, and then developed an anti-anxiety treatment based on reducing neuroinflammation, which I believe may be the root cause of anxiety in many cases. That neuroinflammation-glutamate hypothesis of generalized anxiety disorder is detailed in this 2010 thread.  



#44 gamesguru

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Posted 08 November 2018 - 12:31 AM

yeh that is probably it. inflammation.  I read that curcumin inhibits glutamate release but only by 30% at 6 micromolar.

 

this is 0.000006 mol/L * 368.38 g/mol * 65 L = 143mg of pure unadulterated curcumin for a 65kg male.  that's a lot of turmeric to swallow

 

interestingly 70% inhibition was achieved at just over 10 micromolar.  So perhaps there is clinical significance here to the kitchen spice? idk, maybe if you grind some black pepper in with it, idk

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#45 Hip

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Posted 08 November 2018 - 12:57 AM

 that's a lot of turmeric to swallow

 

People usually equate turmeric with curcumin, but turmeric also contains ar-turmerone, which is thought to reduce microglial activation. See this paper.

 

Also, turmeric reduces gut inflammation, and gut inflammation is known to directly up-regulate brain inflammation by a vagus nerve pathway. 



#46 Hip

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Posted 08 November 2018 - 01:19 AM

this is 0.000006 mol/L * 368.38 g/mol * 65 L = 143mg of pure unadulterated curcumin for a 65kg male.  that's a lot of turmeric to swallow

 

I think you'd need a much higher oral dose of curcumin to achieve a 6 μM concentration in the blood: not only is the bioavailability of curcumin very low (in the order of 1%), but curcumin's plasma protein binding is high at around 98%. Plasma protein binding is the percentage of a drug or supplement which binds to blood proteins and is thus lost (becomes inactive), according to the free drug hypothesis. So you lose 99% of your curcumin through poor bioavailability, and then for whatever does get absorbed into the body, you lose another 98% due to plasma protein binding.


Edited by Hip, 08 November 2018 - 01:21 AM.

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#47 gamesguru

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Posted 08 November 2018 - 01:19 AM

yogurt is also believed to mitigate gut inflammation, however i noticed no apparent benefits with its prolonged use.

 

back to the subject.  turmeric is supposedly 2-3% curcuminoids by weight.  curcumin is taken as the sum total of curcuminoids, nothing more nothing less.  therefore one is 33-50x as potent as the other.

 

what's interesting now is i've read the two aren't so different in the body, presumably due to saturation of the uptake sites, so that turmeric isn't 30x less bioavailable at all!  But classically, 143mg of curcumin equates to 4.7 grams of turmeric, which is an unpleasant amount.  Again however, adding black pepper sways the scales, piperine, a known irritant alkaloid, is also known to enhance curcumin uptake up to 7-20x.   piperine is thought to bind the allosteric site and induce cell signal transduction and efflux pump inhibition of the intestinal villi.  It is not just curcumin. Any drug which uptakes through the lumen and villi is enhanced in its distribution by the common black peppercorn.

 

the plasma binding is an unlikely culprit.  just as much substrate as binds the plasma is likely to dissociate in the brain.  regardless, if only 0.01% of curcumin made it to the brain i doubt we would see such promising science in favor of it


Edited by gamesguru, 08 November 2018 - 01:22 AM.


#48 Hip

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Posted 08 November 2018 - 01:41 AM

 turmeric is supposedly 2-3% curcuminoids by weight.  curcumin is taken as the sum total of curcuminoids, nothing more nothing less.  therefore one is 33-50x as potent as the other.

 

So you are saying that a "curcumin" supplement in fact contains a spectrum of curcuminoids which include curcumin. That may be the case, but I don't think ar-tumerone (aromatic turmerone) is classified as a curcuminoid, it is classified as a sesquiterpenoid

 

This paper for example says:

 

 

two sesquiterpenoids (α-turmerone [AL] and aromatic turmerone [AR]) as well as three curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were isolated from C. longa extract

 

Thus if you buy a curcumin supplement containing curcuminoids extracted from turmeric, it's probably not going to have any of the turmeric sesquiterpenoids such as ar-tumerone.

 

 

In my own tests of turmeric for treating my anxiety symptoms (which as mentioned earlier I think are caused by brain inflammation and the subsequent glutamate release), I found turmeric powder (from a supermarket) more effective than curcumin supplements. So this anecdote suggests that it is the turmeric sesquiterpenoids such as ar-tumerone which have anti-inflammatory benefits as well, and you likely don't get these in curcumin supplements. 

 

Thus people should not think of curcumin as stronger and better than turmeric.

 

 

By the way, in Asian stores in the UK you can buy a kilo of turmeric powder for around £3, so that can work out very economical.


Edited by Hip, 08 November 2018 - 01:45 AM.

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#49 Hip

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Posted 08 November 2018 - 02:00 AM

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 2001 study suggested that quinolinic acid from neuroinflammation is not likely to activate NMDA receptors:

 

 

Our data suggest that, although synthesis of QUIN from activated microglia and invading macrophages can increase its extracellular concentration 10-100-fold, the levels that are reached in these conditions remain far below the concentrations of QUIN that are necessary for excessive NMDA receptor activation.

 

Though this 2012 study suggests it may cause problems. 

 

I have not found any study that says for certain that quinolinic acid from neuroinflammation is able to substantially activate NMDA receptors. 

 

Though I guess in combination with glutamate from neuroinflammation there will be an additive effect on NMDA receptor activation.


Edited by Hip, 08 November 2018 - 02:03 AM.

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#50 gamesguru

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Posted 09 November 2018 - 02:19 AM

i would not put all my eggs in the kynurenine basket.

 

glutamate is the single most influential and abundant neurotransmitter; anyone claiming to have wrapped their heads around it is probably fooling themselves.  They are probably observing the froth on the river and not the river movement itself.  Glutamate is synthesized through about 8 different pathways and it breaks down into over a dozen byproducts.  It's present throughout the entire nervous system, and is vital to many unrelated organs.  It's involved in more brain pathways and at a lower level than anything else, and is a significant player in the course of nearly all mental illness.

 

Of course people will believe anything they read online, so NAC and memantine fads are nothing short of typical.


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#51 Carnation4000

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Posted 12 November 2018 - 12:21 AM

I'm genetically inclined to high glutamate.  Mostly my levels are better now that I'm aware and have modified my diet. 

 

But here are the things I take to help lower my glutamate levels, especially if I'm having insomnia:  Magnolia Bark extract, B6 (P5P), Valerian, Magnesium, Elderberry, Cat's Claw, Niacin, and Olive Leaf.  Magnolia Bark is the thing that really brings down glutamate levels for me.

 

Also, of course, stay away from anything that can turn into glutamate - like theanine or glutamine.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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