GABA powder
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@LucH the lack of obvious BBB crossing apparently doesn't negate GABA effects , the basic reason I say that is that gut bacteria producing GABA have been measured to have distinct effect on whole organism
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@sunsunsun I think the trademarked pharmaGABA at least has some evidence behind it that shows it can exert parasympathetic action, possibly via the vagus nerve.
https://pubmed.ncbi.nlm.nih.gov/30263304/
https://pubmed.ncbi.nlm.nih.gov/16971751/
https://www.tesble.com/10.1002/biof.5520260305The latter study found that 100 mg PharmaGABA produced better results than l-theanine (200mg) as regards alpha brain waves and beta brain waves, though both interventions produced favorable changes.
GABA also prevented the decrease in Immunoglobulin A levels (a marker of immune suppression) when subjects were exposed to a stressor (walking a pedestrian bridge when they were afraid of heights) compared to placebo.
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@jamezb46 apparently the pharmagaba is a psyop and normal synthetic gaba has the same effect. pharmagaba is produced by microbial fermentation which shouldn't change how the actual end-product works. a gaba researcher actually called them out on it in a submission to a journal or whatever. microbial fermentation to produce pharmaceuticals/supps is actually neat and i have nothing against it.
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@sunsunsun Perhaps, but it's possible that the GABA not produced by fermentation has unnatural ratios of the various conformations that GABA can exist in.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 said in GABA powder:
Perhaps, but it's possible that the GABA not produced by fermentation has unnatural ratios of the various conformations that GABA can exist in.
I'd would express it on another way.
Gut bacteria known to metabolize or grow on GABA
A number of gut microbes possess the GABA shunt (gad/gab genes), allowing them to use GABA for growth, energy production, or acid resistance.Improve transit (MMC) to avoid most of the problems due to excess. No GABA supplement if suspicion of candidiasis.
@sunsunsun
I've just finished writing an article on why GABA powder is useful for the microbiota. Not yet posted. Need coffee
Thanks for contributing: I didn't know (...). -
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I would strongly advise against relying on Chat GPT to get your knowledge. It is frankly abysmal at chemistry. I have asked it specific questions that it gets completely wrong, referring in its answer to completely different molecules.
Here are some excerpts from the paper that my claim came from:
https://www.sciencedirect.com/science/article/pii/0166128088800848?via%3Dihub
"It is believed that the conformational behaviour of GABA and GABA inhibitors is a critical factor for their selective biological property. Experimental analysis on GABA, viz., X-ray crystallography [6-8], IR [9,10] and 1H-NMR spectroscopy [ 11 ], suggest that this amino acid exists mainly as a zwitterion in solid and gaseous state or in solution. Theoretical conformational analysis [12-16] of the isolated molecule predicted the lower energies for the folded conformer with a rotational barrier greater than 40 kcal mol- 1 for the extended conformer.
"Theoretical calculations involving solvent effects [ 13,15,17 ] have
shown that this rotational barrier is largely reduced in solution. Dipole moment measurements [18,19] favour the fully extended form whereas crystallographic evidence [6-8] supports a conformer which is not fully extended.""Results of ~H-NMR measurements [11], on the other hand, predicted the existence of at least five extended and folded conformers in solution. The biological importance of the GABA conformation (i.e., the biologically active conformer) has been stressed by studies on the stereospecificity of GABA analogues [20-24]. For example, muscimol [25], a potent GABA agonist with respect to neuronal receptors, corresponds to a partially extended form of GABA
[24]. On the other hand, a wider range of conformers have been proposed to be the active forms at the perisynaptic uptake system [20,22,24 ]"So, at least according to this paper, the particular effects that a particular GABA analogue has can be explained by whether the analogue resembles the extended or the folded conformation of GABA.
That implies that endogenously, there is a meaningful difference between the folded vs the extended form of GABA (if the authors are correct the folded vs extended forms have different affinities at GABA-A vs GABA-B receptors).
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@jamezb46 said in GABA powder:
Here are some excerpts from the paper that my claim came from:
https://www.sciencedirect.com/science/article/pii/0166128088800848?via%3Dihub
"It is believed that the conformational behaviour of GABA and GABA inhibitors is a critical factor for their selective biological property. Experimental analysis on GABA, viz., X-ray crystallography [6-8], IR [9,10] and 1H-NMR spectroscopy [ 11 ], suggest that this amino acid exists mainly as a zwitterion in solid and gaseous state or in solution. Theoretical conformational analysis [12-16] of the isolated molecule predicted the lower energies for the folded conformer with a rotational barrier greater than 40 kcal mol- 1 for the extended conformer.
"Theoretical calculations involving solvent effects [ 13,15,17 ] have
shown that this rotational barrier is largely reduced in solution. Dipole moment measurements [18,19] favour the fully extended form whereas crystallographic evidence [6-8] supports a conformer which is not fully extended.""Results of ~H-NMR measurements [11], on the other hand, predicted the existence of at least five extended and folded conformers in solution. The biological importance of the GABA conformation (i.e., the biologically active conformer) has been stressed by studies on the stereospecificity of GABA analogues [20-24]. For example, muscimol [25], a potent GABA agonist with respect to neuronal receptors, corresponds to a partially extended form of GABA
[24]. On the other hand, a wider range of conformers have been proposed to be the active forms at the perisynaptic uptake system [20,22,24 ]"So, at least according to this paper, the particular effects that a particular GABA analogue has can be explained by whether the analogue resembles the extended or the folded conformation of GABA.
That implies that endogenously, there is a meaningful difference between the folded vs the extended form of GABA (if the authors are correct the folded vs extended forms have different affinities at GABA-A vs GABA-B receptors).
interdasting...
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@sunsunsun The paper could absolutely be wrong, or I could be misinterpreting it, but that was my impression, anyway.
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@sunsunsun said in GABA powder:
the lack of obvious BBB crossing apparently doesn't negate GABA effects , the basic reason I say that is that gut bacteria producing GABA have been measured to have distinct effect on whole organism
How is GABA powder useful for microbiota?
GABA → succinate → butyrate pathway: The Microbial Power Route.
How gut bacteria convert GABA through the shunt and succinate pathway to fuel and protect colonocytes of the linen walls.Many Bacteroides can use GABA as a carbon and nitrogen source for growth. Some other intestinal bacteria can use an alternative pathway, called the GABA shunt.
GABA is not a preferred primary carbon source for most gut bacteria as growth is usually stronger on sugars or amino acids like glutamate. But when the main fuel is rationed or when an access route is blocked, an alternate pathway is used. Survival, no longer growing and extending.
Butyrate is the star among SCFAs (with propionate) as it upregulates the tight junction proteins (occludin, claudin-1 and -4and ZO-1 (zonulin): Tight junction expression, anti-inflammatory signaling (via HDAC inhibition) and hypoxic barrier maintenance (via oxygen consumption in colonocytes). Butyrate literally energizes the gut barrier.
Even if butyrate is the primary fuel for colonocytes, allowing them to function optimally and maintain the physical barrier, you won’t have rich-butyrate food (butter) arrive at destination.
Food butyrate doesn’t substitute for microbially produced butyrate in the colon. You need help from the microbiota. Dietary butyrate has systemic anti-inflammatory benefits, may support mitochondrial function and is easy on digestion. But dietary butyrate won’t rebuild a damaged gut barrier the way endogenous microbial butyrate does.
Also, pamper your commensal bacteria with a varied supply of useful nutrients...
Butyrate is indirectly enhanced by resistant Starch (potato, rice, bread), Inulin (FOS from onions, garlic, asparagus, bananas, leeks), pectin (apple, citrus fruit, carrot), beta-glucan (oat, mushroom), GOS ((legumes, dairy), XOS (fruits, vegetables, whole grains) when the commensal bacteria feeds on these elements. + Yogurt & Kefir…
Note that the GABA shunt requires enzymatic reactions: GABA → Succinate = substrate for some bacteria that convert it into butyrate, a key SCFA. It serves as a signaling molecule that modulates immune and epithelial cell activity.
As you know probably, SCFAs—especially butyrate and propionate—upregulate junction proteins:
ï€ Occludin
ï€ Claudin-1 and -4
ï€ ZO-1 (zonulin)
Result:
✓ Reduced gut permeability
✓ Less endotoxin (LPS) crossing into the bloodstream
✓ Lower systemic inflammation
More info on this link:
https://mirzoune-ciboulette.forumactif.org/t2153-english-corner-how-is-gaba-powder-useful-for-microbiota#30480 -
@LucH said in GABA powder:
microbiota
Viral episodes since 2020 seem to have had a dramatic (and lingering) negative effect on the oral and digestive microbiome.
Although scientific studies seem to be largely contradictory, I would suggest that Lactic Acid producing bacteria have increased and GABA producing bacteria have decreased.
For me, this has resulted in apparent abdominal sensitivity to pain and swelling, and episodes of digestive motility blockage. 200-400mg/d GABA powder has a relaxing effect on the nerves and muscles involved in the tension/distension.
At the same time, I find that I have to limit Lactic Acid producing foods: fermented ingestibles: no Kimchi, Sauerkraut, Kefir, Buttermilk, Yogurt.
And no Lactobacillus Probiotics. -
@atlee said in GABA powder:
200-400mg/d GABA powder has a relaxing effect on the nerves and muscles involved in the tension/distension.
Yes, indeed but I won't take gaba powder, nor glycine when there is dysbiosis (overgrowth) or unbalance in the microbiota. Why?
let's take 2 strains; E. Coli and candida albicans. They can feed on derived molecules. Make a search with the gaba shunt if you want more details.
I've explained this pathway in details on my forum.
When suffering from overgrowth, the tactics isn't the same.
In summary: Weaken – kick and push out.
Coordinated and planned tactic, which results in a structured scheme:
ï€ Weaken (deprivation of resources but not complete abstinence)
ï€ Organize to knock out (limiting the ability to adapt)
ï€ Machin-gun (with increased die-off) + assistance to evacuate LPS endotoxins
ï€ Consolidation (nutrients useful to ensure diversification of commensal bacteria + enhancing peaceful communication through the vagal nerve between the brain and the stomach).
Occupy the place (diversified menus and possible contributions of specific strains depending on the terrain, e.g. if you suffer from allergies / histamine intolerance or not.In prevention, get informed on motility (MMC) if your transit is lazy.
Need 30 g fiber (progressive) from veggies and fruits, as a substrate.
To set things in order, before it's too late: Quercetin, iodine (with a protocol to open NIS symporters and avoid a Wolff-Chaikoff effect).
If in crisis, I'd proceed with essential oils. I did it last year with success, when my transit was rather lazy, with flatulencies and sulphur odors. Details are to be found in my log, on my forum (In French; translator needed). Under control. Have still to take care for histamine excess. I manage rather well, though this last point is not ideal. -
Great summary and suggestions. I spent a lot of my RPF years in this neighborhood, and I am very much aligned with your views.
I would add to my post that I have had good success with taking half of my 200-400mg/d GABA powder sublingually. It seems to have very significant sublingual uptake, perhaps by avoiding the gut microbiome. -
So my own experience is that it works and definitely reaches the brain. It will probably help if you are suffering from depression and/or recovering from taking SRIs like Haidut suggested in one interview but it won't have any "general" health effect, it's not some nutrient you would be deficient in. It just makes you very relaxed after a few hours.
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@pittybitty >no general health effect
he doesn't know
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@sunsunsun ???
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@pittybitty there's probably dozens of studies showing it is probably beneficial for overall general health
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@sunsunsun High GABA means serotonin is low, it's probably that.
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@pittybitty you're one of those people who can't bring themselves to concede a point aren't you?
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@pittybitty I was reflecting on the significance of whether oral GABA penetrates the CNS or not and I'm not sure
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even if it can if it can substantially and persistently elevate GABA-ergic signaling directly in the CNS
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if it can't why that would be any significant evidence that it could not nevertheless produce a state of calm that indirectly influences the whole organism and hence the CNS
To give an analogy, consider massage. I (and many others) find massage to be very relaxing. Does massage "directly and persistently elevate GABA-ergic signaling in the mammalian CNS". Well, no. Obviously not.
Does that mean it can't produce calmness that does indirectly influence the brain and spinal cord? No. It obviously does.
The heart and digestive system both have GABA receptors, so even if oral GABA is not CNS-penetrant, who cares? If the heart and gut have enhanced inhibitory tone as a consequence of the oral GABA, surely the brain will register that and be more at ease, and that's not even factoring in the influence of the gut on the CNS via the vagus nerve.
In summary, I'm not sure if the "CNS-penetration or bust" paradigm even makes sense for the same reason that massage clearly has CNS effects without those effects being "direct".
In time there is life but no knowledge; outside time there is knowledge but no life
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