Glycine - advice please?

[YippeeKi YOW !!]

@xploit316
I've found that most supps in capsules, even if I dont use the capsule but empty the contents out, dont seem to function the same way the same thing in a tablet form does. Why this is, considering the stuff that goes into making a tablet or a pill cohere, is a mystery.

There are close to a dozen reasonably easy to find types of mag. The ones to avoid are mag citrate ((citrate isn't Vit C or anything in the citrus family, it's part of the Krebs cycle, sometimes called the citric acid cycle, that produces and supports glutamate as part of the lengthy conversion process) and mag oxide, which is used by most people as a safe and non-intestinally damaging laxative. It also has the lowest amount of bioavailable magnesium, at about 4% bioavailability/absorption.

There's mag threonate, mag-taurate, mag bisglycinate, mag orotate, mag carbonate, mag chloride, mag gluconate (carbonate, chloride and gluconate are reported to cause diarrhea at even reasonable levels, so probably good to avoid), mag malate, mag aspartate (mag bound to aspartic acid, which is one of two components that form aspartame, a highly excitotoxic sweetener, so I'd avoid), mag bicarbonate, mag hydroxide, mag lactate (bound to lactic acid), mag trisilicate ..... I'm probably missing a few, but you can see that you have your work cut out for you in terms of researching your various options.

I'm sad that the mag glycinate didnt work for you, but then it was a different form from the mag gly I had success with. Who knows what tiny little molecular deviation might make the difference.

I'd also be careful with lithium orotate and do your due diligence before you start taking it. It can produce some powerful reactions, not all of them good, and dosage amount is really important.

I had no success with anything that claimed to help with the conversion of glutamate to GABA. The only thing that worked for me was finding a way to block the activity of glutamate and the over-charged, over-firing NMDA receptors while my brain and neuro system had a chance to heal and rebalance on their own.

GABA supps don't cross the BBB in any amount that might make a difference and some of them dont cross it at all, unless you have a leaky BBB to begin with, and that's a whole different problem .

It's hell having a touchy system, and I sympathize. You're going to have to cut your own path thru that personal jungle.

I hope I've given you some starting points, and I can't encourage you enough to know that there's an answer out there for your particular needs, you just have to keep plugging away til you find it. It took me a long, painful time. Hopefully, your path will be clearer and quicker, and that others will chime in with their input and knowledge til you find the key.

Onward and upward !!!!

EDIT FOR PS: If you highlight a portion of the post you're responding to and then hit 'Reply'', you won't have to quote the whole post, just the highlighted portion. If you just hit 'Reply' without highlghting anything, the entire post you're responding to will appear in your answer window. It makes for some very long threads, especially when the answers are, like mine was, pretty windy to start with .

 

[pamojja]

The ones to avoid are mag citrate and mag oxide, which is used by most people as a safe and non-intestinally damaging laxative. It also has the lowest amount of bioavailable magnesium, at about 4% bioavailability/absorption.

In in an further adempt to help other cut down on cost of supplements and internet myths - but not bioavailabilty - my past response to your assumption again. Still not tired of copying/pasting..

Magnesium oxide has very low bioavailability, about <4%. I find it most useful for constipation, but not for anxiety.

I'm getting tired typing it out again and again for so many years , therefore just copied it from an other forum:

When I read this post by niner in 2013 I already had tried all different types of oral Mg supplements due to very severe painful-muscle cramps (Magtein too) for years. Since I didn't found much improvement with any of the distinct forms, due to niner's post I also started to use cheap Mg-oxide. And indeed, just the elemental total Magnesium amount supplemented a day would result in a somewhat alleviation of the symptom.

By which I don't want to discourage you to experiment yourself with all the different form, in the end we are all different with different preconditions and bio-chemical individuality. Some really might work better in your case. And different forms are indeed differently tolerated by each of us. For example the 2.5 g/d of elemental Magnesium I tolerate might cause diarrhea already at only a tiny fraction in any other.

Just in my case I could have saved myself a lot of money by using the cheap types right away. In the end only Mg-sulfate infusions I've got since November last year, ceased my muscle-cramps completely

But I don't have anxiety.

And of course again, everyone is different and reacts differently to different Mg-compounds. So if a particular causes more diarhea than an other, then of course avoid it. But in my case I found no difference in laxative effects.

 

[YippeeKi YOW !!]

@pamojja

In in an further adempt to help other cut down on cost of supplements and internet myths - but not bioavailabilty - my past response to your assumption again. Still not tired of copying/pasting..

These are not my assumptions. These represent well-established, tested and proven knowledge regarding the various forms of mag and their functions in the human body.

Like you, I do get tired of defending posts, but here goes, re: magnesium supps, which your body apparently reacts to quite differently from the most others:

Magnesium Oxide
Magnesium oxide is one of the least absorbed forms, but because the oxide molecule is small and compact, it delivers one of the highest percentages of elemental magnesium per dose, making it an effective choice for someone who wants to take as few capsules as possible. Because it is not as quickly absorbed in the intestine, magnesium oxide has more osmotic (water-attracting) effects in the colon, providing support for those with occasional constipation.*

Magnesium Glycinate
Magnesium glycinate is a gentle form for individuals who are sensitive to magnesium oxide or citrate, as it is less likely to cause a laxative effect. In this form, magnesium is bound to glycine, a non-essential amino acid involved in protein synthesis and transmission of chemical signals in the brain. Glycine is considered a relaxing neurotransmitter and may enhance magnesium’s natural calming properties. This could be one of the best types for those who want to promote mental calm, relaxation and good quality sleep.

Magnesium Malate
Another gentle form for those sensitive to magnesium oxide or citrate, is magnesium malate. It is often recommended for people suffering from fatigue and symptoms of fibromyalgia, since malic acid - a natural fruit acid present in most cells in the body - plays a key role in ATP synthesis and energy production.

Source: Vital Nutrients

There are dozens and dozens of internet sites and research papers supporting the use of Mag Oxide and Mag Citrate as laxatives. Because I only have a brief window of both energy and focus, I encourage anyone considering mag supps to do some quick googleing to determine whch type is best for whatever they're dealing with.

As far as cost goes, if you've ever dealt with extreme, wracking anxiety, you'll know that $18 for an approx 2-6 months supply, depending on how much you're using, is a miniscule price when balanced against the benefits.

I buy bulk powder forms, which are incredibly cheap, especially for the oxide and citrate mags. I use the more expensive Solgar mag gly because it savd my life and sanity, and I'm very familiar with its functional mechanism and effect in my body.

My avoidance of mag citrate has nothing to do with cost or effectiveness, but rather with the binding to citrate, which, as part of the Krebs cycle, goes thru several dozen conversions, including to free glutamic acid, which is extremely unpleasnt in its effects to those of us sensitive to it.

I think it's terrific that the cheapest form of mag works for you, but as you yourself said, we're all different in terms of what will or wont be effective on our systems.

I'm going to bookmark this post so I don;t have to keep rebutting the same arguments over and over, from scratch. A girl gets weary, doncha' know.

 

[leela]

Just for general info, since I don't see it mentioned above, there is also the option of Mag Threonate.
I used the glycinate form for years, but in the last year or so switched to threonate for various reasons pertinent to my personal circumstance:
https://www.ncbi.nlm.nih.gov/pubmed/24077207

 

[YippeeKi YOW !!]

@leela

Just for general info, since I don't see it mentioned above, there is also the option of Mag Threonate.

It was the first one I mentioned ....

There's mag threonate, mag-taurate, mag bisglycinate, mag orotate, mag carbonate, mag chloride, mag gluconate (carbonate, chloride and gluconate are reported to cause diarrhea at even reasonable levels, so probably good to avoid), mag malate, mag aspartate (mag bound to aspartic acid, which is one of two components that form aspartame, a highly excitotoxic sweetener, so I'd avoid), mag bicarbonate, mag hydroxide, mag lactate (bound to lactic acid), mag trisilicate

How differently does the threonate version express in your system and in what way? It could be helpful for others reading this .... it tends to be expensive, so having a good idea of what it can do could make the difference for someone considering it.

Thank you for the input re threonate, esp since I dont have any experience with to pass along and share.

 

[leela]

It was the first one I mentioned ....

Sorry, I have the serious Dumbs today, with another migraine coming on...

I can't say the difference is hugely blatant in my experience. But the TNFa thing is an issue with me, as well as neuropathic pain, so on my doc's recommendation I've switched to it. I defo notice a difference when I skip it,
so it's doing something good

Sorry I can't be more technical than that

 

[pamojja]

These are not my assumptions. These represent well-established, tested and proven knowledge regarding the various forms of mag and their functions in the human body

Source: Vital Nutrients

There are dozens and dozens of internet sites and research papers supporting the use of Mag Oxide and Mag Citrate as laxatives. Because I only have a brief window of both energy and focus, I encourage anyone considering mag supps to do some quick googleing to determine whch type is best for whatever they're dealing with.

The only way to know for sure is actually look at the studies and their contradicting studies where such assumption are made. Even if there are dozen and dozens of studies, one has to look at each for its own merrit. But gladly (or should I say sadly?) with Mg-absorbtion, you wont find that many.

Maybe I've should made it clearer my experience only confirmed what someone I mentioned as niner in my post, just did. I'll just paste it in todo for you to read here:

Posted 14 February 2013 - 03:31 PM

It's a myth that mag oxide is poorly absorbed. The source of the myth was a 2001 paper by Firoz and Graber, which used very short-term urine collection, and came to the erroneous conclusion that the fractional absorption of the oxide form was 4%. Coudray et al. in 2005 published a study that used long term collection, and found that the oxide bioavailability was quite good. Better even than some of the organic forms. Gluconate was the best, in their study. Looking at Plasma Mg, RBC Mg, and Bone Mg at the end of the experiment, no significant difference was found from any form. The Coudray paper has free text, but the headings are buggy in their HTML tables, so be sure to take note of that if you read it. This post may also be interesting.

The bottom line is that there isn't much point in looking for the "best" form of magnesium, because they are all pretty similar in the end. Look at the RBC and Bone magnesium- that's what counts. Oxide has the highest magnesium density of any form by far, so it doesn't require multiple pills, or even a large one. It's also one of the least expensive, and it's quite well tolerated. You should find a form that agrees with your digestive tract and your wallet, and don't bother obsessing over it. If you are looking for special effects like increasing brain Mg, then you will probably want to consider exotic forms like threonate, but be prepared to take a lot of caps.

The supplement industry owes a huge debt to Firoz and Graber, since their erroneous conclusion created an entire market segment.

You'll find the only study serving as source of assumption - magnesium oxide only be absorbed at 4% - and can verify its accuracy of lack thereof yourself.

And you'll find the contradicting study, if it is indeed more relyable than the first. And then everone else is enabled in making up one's own mind.

 

[YippeeKi YOW !!]

I’m reposting the link posted above, and highlighting a portion of it below the link here. https://www.longecity.org/forum/top...ental-of-magnesium-types/page-3?&#entry545213

The following quote was taken directly from the site linked in the post directly above this one from niners Longecity post, re-posted above. It makes virtually no sense, and contradicts itself in several places. Both its meaning and conclusions are murky. Here’s an example:

“Magnesium can be absorbed from an almost insoluble compound such as magnesium in the human body. Basis of the absorption of magnesium from magnesium oxide is the law of mass action and processes in a dynamic system, such as at the contact point between the chyme and the epithelial cells of the intestine. Magnesium oxide is insoluble in water, but only sparingly soluble in water. It solves the following equation: 2 MgO + H 2 O -> Mg (OH) 2. Because of the equilibrium dissociation constant of this reaction is far on the side of magnesium oxide and water. Once after the above mentioned law primarily gone into solution magnesium is absorbed by the intestinal epithelium, the law of mass action has been disturbed as ever magnesium is removed from the balance. Thus, in the gut immediately released from the magnesium salt, which is absorbed in all areas of the intestine with the water flow. This process is continuous throughout the transit time of Nahrungsbreies who can stomach, intestine and colon take about two to three days. After resorption, which lasts approximately magnesia also two to three days, wherein magnesium citrate but only five hours, it is possible to the human body, magnesium from magnesium oxide actually comparable extent as receive from other compounds.

The absorption of magnesium oxide is not always a gradual continuous process, as stated above. Mg oxide rushes thru your system giving little opportunity for absorption thru the contact of the chime with the intestinal epithelium due to its speed of transit, and rapidly settles in the large intestine where it is an osmotic, hence its excellent laxative effect. Whatever is left of it is expelled fairly quickly from the digestive system when the laxative properties take effect. Very little mg is absorbed during that process, since it passes thru the digestive system so quickly.

Mg glycinate on the other hand, seems to be absorbed, in my experience, at a steady, predictable rate as a result of its being bound to glycine, and provides zero laxative effect (at least for me and multiple others I’ve read in these, and other, threads) which is why it has been so successful in dealing with my various neuro-toxic issues, as I’ve stated before in this and other threads.

Here are a few more sources of information:

Pharmacokinetic Studies of Orally Administered Magnesium Oxide in Rats.
https://www.ncbi.nlm.nih.gov/pubmed/28123145

Magnesium oxide
https://pubchem.ncbi.nlm.nih.gov/compound/14792

Magnesium hydroxide: new insights into the mechanism of its laxative effect and the potential involvement of prostaglandin E2.
https://www.ncbi.nlm.nih.gov/pubmed/1556404

Magnesium
https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

Medical Treatment of Constipation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780140/

[The quality evaluation of magnesium oxide tablet due to acid neutralization action].
https://www.ncbi.nlm.nih.gov/pubmed/15930821

Medical Management of Constipation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348737/

Bioavailability of US commercial magnesium preparations.
https://www.ncbi.nlm.nih.gov/pubmed/11794633

Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652077/

Predicting and Testing Bioavailability of Magnesium Supplements
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683096/


It bears mentioning that the standard pre-op intestinal clean-out used in almost every hospital in the U.S. is mag citrate. It’s also marketed here over the counter as a laxative, with strong warnings attached. A nurse once described its action to me as “Shooting thru you like water thru a fire hose …”

Somewhere in my bulging net files I have a lot more research papers, along with other information of a scientific nature on magnesium in general, and specific types of magnesium and their mechanisms of action (mg citrate and mg aspartate, for instance, are neuro-toxic, exactly the opposite effect I was looking for), but I’m tired, and since you only posted a reference to the above link I re-posted here, embedded in a 7 year old posting by a Longecity member from a thread on that site, which states the posters belief that there’s no difference between the various forms of magnesium marketed OTC, I feel hopeful that these will suffice.

There was also this additional post by pamojja, right under Niner’s on the Longecity site, regarding the problems with the study cited above in purple/lavender:

https://www.longecity.org/forum/top...ental-of-magnesium-types/page-3?&#entry545213
“Don't let this myth (referring to the myth of the uselessness of mg oxide … my comment here for clarity) die to prematurely. It didn't test all available magnesium complexes like malate, glycinate, lysinate, taurinate, threonate..

And then there are practitioners who routinely measure RBC magnesium levels, like Dr. Davis (TrackYourPlaque), who out of their clinical experience recommend malate or glycinate, but not citrate to raise RBC-levels. Exactly such complexes not considered in this study.”


It’s a point well-taken.

It’s also worth mentioning that the cited Coudray/Rambeau study was performed in a lab on rats, not on human subjects in what I’ll call the real world. Significant differences have been found in the results of various studies using lab animals, usually rats, versus in vivo human studies done later .

 

[pamojja]

My reply from that time you mention, was before I experimented with Mg-oxide myself. And found it worked just as good as any Mg-compound already trialed (at the same elemental Mg-amount).

The contradicting quotes originate from a google translation. A much accurate translator especially for scientific texts is https://www.deepl.com. I bolded those sentences again.

A dynamic system

Magnesium can be absorbed by the human body from an almost insoluble compound such as magnesium oxide. The basis for the absorption of magnesium from magnesium oxide is the law of mass action and the processes in a dynamic system, for example at the point of contact between the food paste and the epithelial cells of the intestine. Magnesium oxide is not insoluble in water, but poorly soluble in water. It is solved according to the following equation: MgO + 2 H2O -> Mg(OH)2. Due to the dissociation constants, the equilibrium of this reaction is far on the side of magnesium oxide and water. As soon as the magnesium, which is primarily dissolved in the intestinal epithelium, is absorbed by the intestinal epithelium, the law of mass action is disturbed because magnesium is constantly taken out of equilibrium. Thus magnesium is immediately released in the intestine from the salt, which is absorbed in all areas of the intestine with the water flow. This process takes place continuously during the entire transit time of the food meal, which can last about two to three days through the stomach, intestine and colon. After the absorption time, which lasts about two to three days for magnesium oxide, but only five hours for magnesium citrate, the human body actually succeeds in absorbing magnesium from magnesium oxide to a comparable extent as from other compounds.

Hope this article with a better translation-machine makes more sense now.

Here are a few more sources of information:

Pharmacokinetic Studies of Orally Administered Magnesium Oxide in Rats.
https://www.ncbi.nlm.nih.gov/pubmed/28123145

This study states: "85% is excreted via the feces without being detected in pharmacokinetic analysis." - Without being detected, how they could ever come up with the 85%?

Magnesium oxide
https://pubchem.ncbi.nlm.nih.gov/compound/14792

Its just a endless PubChem article, adding no original science to this subject.

Magnesium hydroxide: new insights into the mechanism of its laxative effect and the potential involvement of prostaglandin E2.
https://www.ncbi.nlm.nih.gov/pubmed/1556404

In this study "each subject took 45 ml containing either placebo or 1,200, 2,400, or 3,600 mg of Mg(OH)2 plus 240 ml of water." - if one uses the same amounts of elemental magnesium as other Mg-compounds, the results would certainly be laxative to the same extent too.

Magnesium
https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

No original work to verify.

Medical Treatment of Constipation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780140/

About laxative action of different Mg-salt, but not about absorption.

[The quality evaluation of magnesium oxide tablet due to acid neutralization action].
https://www.ncbi.nlm.nih.gov/pubmed/15930821

Tested the different disolution of 2 Mg-oxide products in water. Nothing about absorption in humans.

Medical Management of Constipation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348737/

Again about laxative action of different Mg-salt as in 2 links above, but also not about absorption.

Bioavailability of US commercial magnesium preparations.
https://www.ncbi.nlm.nih.gov/pubmed/11794633

That's the 2001 paper by Firoz and Graber, already linked to many times in the posts above. With the shortcoming of too short urine-collection time.

Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652077/

No comparison about different Mg-compounts absorption, but the difficulties with those absorption studies:

The absorption of Mg2+ should be studied in human studies by using indirect methods of dietary balance that are based on measuring faecal or urinary Mg2+ excretion after oral Mg2+ administration. However, such chemical balance studies also have a number of limitations. Usually, these studies are carried out over a period of several days or weeks, where a strict diet has to be followed. Long-term balance studies are susceptible to low compliance, and it is questionable whether the results of such long-term balance studies are suitable for extrapolation on bioavailability. These studies instead provide data on the required intake amounts. However, a short balance period may yield inaccurate absorption results because the meals given during the balance period might mix with preceding meals in the intestine, an effect that might vary between subjects due to varying gastrointestinal passage time. At a minimum, probands must be given food low in Mg2+ throughout the studies, especially through beverages (e.g., water). Nevertheless, mineral excretion in faeces cannot be strictly related to intake. In addition, endogenous faecal Mg2+ is lost through bile, the pancreas, and other ways; thus, ‘true absorption’ cannot be determined because there is no ability to distinguish between endogenous and dietary Mg2+.

Predicting and Testing Bioavailability of Magnesium Supplements
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683096/

Only tested magnesium serum levels after 6 hrs, too short a time frame. And not accurate as pointed out in the study just above. With differences in serum levels found not worth mentioning (+6.2% vs. +4.6%).

Somewhere in my bulging net files I have a lot more research papers,..
I feel hopeful that these will suffice.

Please only post research papers which really tested Mg-absorption!

But not as done now - with only the 1 link already pointed out as the original source - and all other links not supporting the opinion of poor 4% Mg-oxide absorption in any way.


We are still not a bid further than having only 2 studies:

1.) The Firoz study in humans with short-term collection of urine only.
2.) The Coudray study tested the absorption in rats after 2 weeks of Mg-repletion in plasma, RBC, and bone.

The first study can't be accurate because it uses misleading urine short-term collection.
The second hasn't been replicated in humans.

With these uncertainties, I simply tested and proved the thesis of the second study at least in myself. Everyone else, can believe either of those 2 thesis. Or test it in oneself too.

That's the only way to bust internet-myths in lack of conclusive studies oneself. And not uneccesarily waste a lot of money.

 

[YippeeKi YOW !!]

[QUOTE="pamojja, post: 2234930, member: 29407"]The contradicting quotes originate from a google translation. A much accurate translator especially for scientific texts is https://www.deepl.com. I bolded those sentences again.[/QUOTE]
It would have been sooooo helpful if you'd posted a link to your second, much better, translation. Wading thru the first on you posted was hard hard work.

I feel like I was sandbagged.

Without being detected, how they could ever come up with the 85%?

Fecal analysis comes to mind.

I'm sorry that the links I posted weren't up to your expectations.

I'm bowing out of this now.

 

[pamojja]

It would have been sooooo helpful if you'd posted a link to your second, much better, translation. Wading thru the first on you posted was hard hard work.

I feel like I was sandbagged.

After googling sandbagged as non-native English speaker, I totally agree .

The perfect term to describe how I felt already before - after having verified even 10 in part very long articles or studies. And found only 2 of them actually being about comparing absorption - on top of it including the one I already mentioned first, and the shortcoming of both.

That was about 10 times as much unfruitful work (as non-native speaker), then the link to the short translated article (with even a link to its german original). Where I also commented:

You'll find the only study serving as source of assumption - magnesium oxide only be absorbed at 4% - and can verify its accuracy of lack thereof yourself.

And you'll find the contradicting study, if it is indeed more relyable than the first.

Not about the link to a translated piece of expert-opinion at all.

I'm bowing out of this now.

You might not understand my persistance in verifying relevant studies now. But my only intent is that with all my efforts in proving this internet-myth about poor 4% Mg-oxide bioavailabilty wrong (and only supplement companies profit from) - at least some will verify by themself. And can safe some money.