Oral Exposure To The Free Amino Acid Glycine Inhibits The Acute Allergic Response In A Model Of Cow'

LeeLemonoil

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https://www.sciencedirect.com/science/article/pii/S0271531718300095

Abstract

The conditionally essential amino acid glycine functions as inhibitory neurotransmitter in the mammalian central nervous system. Moreover, it has been shown to act as an anti-inflammatory compound in animal models of ischemic perfusion, post-operative inflammation, periodontal disease, arthritis and obesity. Glycine acts by binding to a glycine-gated chloride channel, which has been demonstrated on neurons and immune cells, including macrophages, polymorphonuclear neutrophils and lymphocytes. The present study aims to evaluate the effect of glycine on allergy development in a cow's milk allergy model. To this end, C3H/HeOuJ female mice were supplemented with glycine by oral gavage (50 or 100 mg/mouse) 4 hours prior to sensitization with cow's milk whey protein, using cholera toxin as adjuvant. Acute allergic skin responses and anaphylaxis were assessed after intradermal allergen challenge in the ears. Mouse mast cell protease-1 (mMCP-1) and whey specific IgE levels were detected in blood collected 30 minutes after an oral allergen challenge. Jejunum was dissected and evaluated for the presence of mMCP-1-positive cells by immunohistochemistry. Intake of glycine significantly inhibited allergy development in a concentration dependent manner as indicated by a reduction in; acute allergic skin response, anaphylaxis, serum mMCP-1 and serum levels of whey specific IgE. In addition, in-vitro experiments using rat basophilic leukemia cells (RBL), showed that free glycine inhibited cytokine release but not cellular degranulation. These findings support the hypothesis that the onset of cow's milk allergy is prevented by the oral intake of the amino acid glycine. An adequate intake of glycine might be important in the improvement of tolerance against whey allergy or protection against (whey-induced) allergy development.
 

LeeLemonoil

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Vitamin A also attenuates the allerigic effects, cant find the study but i posted it here. Maybe high Glycine and Retinol availability were a factor in evolution of milk-tolerance.
 

Mossy

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It's good to know this, as a remedy for allergic reactions. I find that supplementing with the isolated amino acid glycine makes me very lethargic and flat. It may be best to get this by way of gelatin--if that would work.
 
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It's good to know this, as a remedy for allergic reactions. I find that supplementing with the isolated amino acid glycine makes me very lethargic and flat. It may be best to get this by way of gelatin--if that would work.

Possibly, although you'd need a bit more since gelatin is 35%-40% glycine for bovine and porcine varieties.

4 grams of glycine even when taken with 40 grams of protein + some fruit made me heavily stoned for half a day. Jello made with 300ml orange juice and 10g porcine gelatin eaten with 40 grams of protein + some fruit also sedated me, although far less aggressively and only until the afternoon, when eaten in the morning. The same amount of jello eaten in the evening was effective in setting the mood for bed.
 

Mossy

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Possibly, although you'd need a bit more since gelatin is 35%-40% glycine for bovine and porcine varieties.

4 grams of glycine even when taken with 40 grams of protein + some fruit made me heavily stoned for half a day. Jello made with 300ml orange juice and 10g porcine gelatin eaten with 40 grams of protein + some fruit also sedated me, although far less aggressively and only until the afternoon, when eaten in the morning. The same amount of jello eaten in the evening was effective in setting the mood for bed.
Yes, that has been my experience as well, with supplemental glycine—totally wipes me out—whereas gelatin sedates, but not like the supplement. What about pork rinds? Looks like a single 14g serving (9 grams total protein) would have about 1670mg glycine. I know some don’t like the fat content, but it’s primarily saturated.
 
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Yes, that has been my experience as well, with supplemental glycine—totally wipes me out—whereas gelatin sedates, but not like the supplement. What about pork rinds? Looks like a single 14g serving (9 grams total protein) would have about 1670mg glycine. I know some don’t like the fat content, but it’s primarily saturated.

In principle I'm a fan of any high gelatin animal part; however, I shy away from pork, partly ever since I read this article-- http://perfecthealthdiet.com/2012/02/the-trouble-with-pork-part-3-pathogens/-- and partly for lack of a good marinade recipe. I only use porcine gelatin until my shipment of bovine gelatin arrives because supermarkets offer no alternative.

Big saturated fat fan, especially from ruminant animals.

Not sure how much gelatin is in ground beef, goat, and lamb but I rotate those 6x/week and it never gets old.
 

BigChad

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Possibly, although you'd need a bit more since gelatin is 35%-40% glycine for bovine and porcine varieties.

4 grams of glycine even when taken with 40 grams of protein + some fruit made me heavily stoned for half a day. Jello made with 300ml orange juice and 10g porcine gelatin eaten with 40 grams of protein + some fruit also sedated me, although far less aggressively and only until the afternoon, when eaten in the morning. The same amount of jello eaten in the evening was effective in setting the mood for bed.

@Mossy any idea why glycine does this? I had to switch from magnesium bisglycinate to aspartate due to the bisglycinate causing insomnia when taken at night followed by massive fatigue the next day.
 

Terma

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Not related to the OP (is good), but: I've had problems with glycine, meaning taking 3g, sleeping for 3 hours before becoming wide awake for the rest of the night, and it didn't seem to be my blood sugar.

My most significant thought was that glycine - either through creatine synthesis, or through soaking up methyl groups via GNMT *if* it was low enough in liver to matter - could indirectly take methyl groups away from HNMT (histamine breakdown). The problem with that is quantification.

One case where this could happen is if you have a retinoic acid overload in your liver - either because of too much retinoic acid or because of not enough CYP26 or NADPH; in this case the RA upregulates GNMT and logically should process/require more glycine and soak up methyl in the process.

But I can't help but feel it's more realistic for it to be its NMDA receptor agonism or chloride channel actions. NMDA can definitely and very immediately mess with sleep.

Another possibility is that glycine only really works right in conjunction with other inhibitory neurotransmitters and receptors, so being low in any of them might mess stuff up: GABA(A/B), endocannabinoids, maybe oleamide, maybe kynurenic acid or xanthurenic acid, maybe something I'm forgetting... It's clear that glycine and chloride channels are important at night to engage full sleep mode in conjunction with GABAA and GABAB; you need all 3.

Endocannabinoids most notably help stop NMDA pre-synaptically at least in some brain areas (unsure of distribution), and I generally don't have problems when taking glycine with THC, so that could be a hint.

Yet another possibility is that the kidneys either recycle too much or too little glycine into serine. Serine is important to the brain relating to NMDA or others (I forget) as well as for phosphatidylserine synthesis [Edit: actually this last part might not happen directly this way because phosphatidylserine is synthesized via base exchange, I forgot this].

It might also need to work in conjunction with another amino acid (histidine, lysine, ...) to work properly. Some of these don't behave as you might think (I sometimes sleep well on histidine, but I think this might be only as long as you have a full protein dinner containing methionine, methyl, etc.).

Finally, high glycine is likely to contribute to ammonia and byproduct load through the glycine cleavage system. Iirc glycine cleavage also requires lipoic acid and some other cofactors, so it could drain something.

There just isn't much in the literature about this topic. Health resources don't grow on trees.

[There is even more stuff relating to chloride channels and their particularities, maybe even bicarbonate, or sodium/potassium/calcium, but am not refreshed on that stuff]
 
Last edited:

BigChad

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Not related to the OP (is good), but: I've had problems with glycine, meaning taking 3g, sleeping for 3 hours before becoming wide awake for the rest of the night, and it didn't seem to be my blood sugar.

My most significant thought was that glycine - either through creatine synthesis, or through soaking up methyl groups via GNMT *if* it was low enough in liver to matter - could indirectly take methyl groups away from HNMT (histamine breakdown). The problem with that is quantification.

One case where this could happen is if you have a retinoic acid overload in your liver - either because of too much retinoic acid or because of not enough CYP26 or NADPH; in this case the RA upregulates GNMT and logically should process/require more glycine and soak up methyl in the process.

But I can't help but feel it's more realistic for it to be its NMDA receptor agonism or chloride channel actions. NMDA can definitely and very immediately mess with sleep.

Another possibility is that glycine only really works right in conjunction with other inhibitory neurotransmitters and receptors, so being low in any of them might mess stuff up: GABA(A/B), endocannabinoids, maybe oleamide, maybe kynurenic acid or xanthurenic acid, maybe something I'm forgetting... It's clear that glycine and chloride channels are important at night to engage full sleep mode in conjunction with GABAA and GABAB; you need all 3.

Endocannabinoids most notably help stop NMDA pre-synaptically at least in some brain areas (unsure of distribution), and I generally don't have problems when taking glycine with THC, so that could be a hint.

Yet another possibility is that the kidneys either recycle too much or too little glycine into serine. Serine is important to the brain relating to NMDA or others (I forget) as well as for phosphatidylserine synthesis.

It might also need to work in conjunction with another amino acid (histidine, lysine, ...) to work properly. Some of these don't behave as you might think (I sometimes sleep well on histidine, but I think this might be only as long as you have a full protein dinner containing methionine, methyl, etc.).

Finally, high glycine is likely to contribute to ammonia and byproduct load through the glycine cleavage system. Iirc glycine cleavage also requires lipoic acid and some other cofactors, so it could drain something.

There just isn't much in the literature about this topic. Health resources don't grow on trees.

[There is even more stuff relating to chloride channels and their particularities, maybe even bicarbonate, or sodium/potassium/calcium, but am not refreshed on that stuff]

Ive gotten the same wide awake sleep effect you described, from just 100mg magnesium glycinate which has 700mg glycine.

Could there be an issue with the way glycine is produced nowadays? Some impurities?
People seem to get the same issue with gelatin.
Are you saying too much vitamin A in the body is responsible for glycines negative effects
 

Terma

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The retinoic acid is only one possibility. I kinda doubt it applies to me, and it concerns mainly the activated form, not necessarily retinol. But there aren't that many modulators of GNMT so it's the first that comes to mind. Maybe even other processes glycine is involved in could steal methyl groups, and it's tempting to entertain that notion because of histamine and HNMT in the brain.

Another possibility, to tie it to the OP: since glycine has immune modulating effects, maybe a strong but temporary silencing through the chloride channels of immune cells (e.g. macrophages, mast cells?[, or even immune cells - or even bacteria - in the intestine?]) might lead to a rebound of immune activity - and maybe also mast cell degranulation and/or histamine release - a certain time later. You'd have to check the time course in those experiments to see if at least we're on the right scale.

Perhaps there might be 2 overlapping effects to glycine happening in that case: a short 3-hour strong inhibitory signal that comes with with a bang but dies quickly, while in the background there's another less prominent but pro-excitatory effect that's more constant or with a different progression - but that lasts longer than 3 hours, and so then once the first signal is gone - that compensated for this second effect - you're left with an excitatory signal relative to normal. Just a possibility, but glycine has a lot of actions... As a sort of (not exactly) example, if glycine antagonized HNMT through lowering methylation somehow, that could conceivably have longer-acting effects than its sedating effects through chloride channel activation (not sure), leading to a histamine rebound. But I'm not convinced this one could happen yet. In some ways an immune (re-)activation seems more plausible, and it could even involve mast cells releasing histamine.
 
Last edited:

BigChad

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The retinoic acid is only one possibility. I kinda doubt it applies to me, and it concerns mainly the activated form, not necessarily retinol. But there aren't that many modulators of GNMT so it's the first that comes to mind. Maybe even other processes glycine is involved in could steal methyl groups, and it's tempting to entertain that notion because of histamine and HNMT in the brain.

Another possibility, to tie it to the OP: since glycine has immune modulating effects, maybe a strong but temporary silencing through the chloride channels of immune cells (e.g. macrophages, mast cells?[, or even immune cells - or even bacteria - in the intestine?]) might lead to a rebound of immune activity - and maybe also mast cell degranulation and/or histamine release - a certain time later. You'd have to check the time course in those experiments to see if at least we're on the right scale.

Perhaps there might be 2 overlapping effects to glycine happening in that case: a short 3-hour strong inhibitory signal that comes with with a bang but dies quickly, while in the background there's another less prominent but pro-excitatory effect that's more constant or with a different progression - but that lasts longer than 3 hours, and so then once the first signal is gone - that compensated for this second effect - you're left with an excitatory signal relative to normal. Just a possibility, but glycine has a lot of actions... As a sort of (not exactly) example, if glycine antagonized HNMT through lowering methylation somehow, that could conceivably have longer-acting effects than its sedating effects through chloride channel activation (not sure), leading to a histamine rebound. But I'm not convinced this one could happen yet. In some ways an immune (re-)activation seems more plausible, and it could even involve mast cells releasing histamine.

So glycine intake increases histamine and mops up methyl groups, basically like niacin or niacinamide?
Do you notice histamine intolerance symptoms after having glycine
 

Mossy

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@Mossy any idea why glycine does this? I had to switch from magnesium bisglycinate to aspartate due to the bisglycinate causing insomnia when taken at night followed by massive fatigue the next day.
I’m really not sure, apart from it being a supplement, not food, and not assimilating with your body as effectively. As many people will note on this forum, isolates may be problamatic as compared to getting these same things via food.
 

BigChad

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I’m really not sure, apart from it being a supplement, not food, and not assimilating with your body as effectively. As many people will note on this forum, isolates may be problamatic as compared to getting these same things via food.

But its odd you mentioned even gelatin had a sedating effect, which makes it seem even food based sources of glycine have this effect.
 

Mossy

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But its odd you mentioned even gelatin had a sedating effect, which makes it seem even food based sources of glycine have this effect.
Yes, a fairly normal sedating effect, but nothing like the wipe out from the supplement glycine.
 
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