Thick as a Brick

[trouble]

Next tool in our hardgainers tool box: glutamine.

This is space saver, but it basically goes like this:


the intenstines of hardgainers, the worrying type, are leaky, and thus don't have what we call tight junctions, what makes them acid and water tight.

You want these cell eges to touch and form a seal against the gut lumen contents..so that uptake is regulated by flux rate (absorption and uptake across the xell membrane.

What controls that?

Glutamine.

Not only that, but glutamine controls the formation of villi, fingerlike projections in the gut that provide a very large highly absorptive surface...magic fingers, tons of them, like a berber rug.

Now, you have poor glutamine production, and not enough in diet to make up the differenxe, you got problems.

Your villi are short, and the slough off, so soon, you got a smmoth gut.

Shitty absorption of nutients.

The NMDA excess from a lack of GABA in liver, might just be what causes some of this irritation of gut as well in hardhainers.

So you got inflamation, poor glutamine induction and maintenance of tight junctions, and you got sloughing and smoothing of the irritated colon.

Slick as a whistle, and about as efficient (or not) for absorption of food.

Okey dokey?

So glutamine is io on them menu.

Next, we're gonna use yet another trick: we're going to help collagen turnover.

And to do that, we're use glutamine, proline, and leucine. Maybe arginine.

Amino acid feeding, via whey shakes.

To read why, drop down to the studies section, my post tonight on muscle cell protein and collagen formation.

They're linked, and the turn of collagen is probably not very good in hardgainers.

At least, in the nervous phenotype.

I'll talk more about this in the next thread.

[Joe]

so is this why some ppl swear by glutamine and others think its fucking junk? when i first used it 3-4 years ago i thought it was the shit. I used it 1.5 years ago and it didnt do DICK (same brand)

[trouble]

Its a matter of whether or not you are deficient in internal synthesis, also in upake and transport that determnes how you will respond to glutamine supplementation.

If you are deficient, then even whey, with its large bolus dose of glutamine and arginine, will not help fill the gap.

If, however, you make concerted changes, supplement diet with extra glutamine - improve Nitrogen - urea cycle chemistry, change muscle stimulation patterns, maybe improve sleep and reduce stress (learn to relax), you will find that as muscle and collagen synthesis are turned on, and energy is dedicated to mass building intead of mostly energy production (mass burning),. Some of the errant mechanisms begin to correct themselves, like gut morphology, and nutrient absorption, and collagen turnover rates, glycogen sytnthesis and fat storage return to more normal stoichiometry (balance).

In short, you begin to function more like a mesomorph and less like an ectomorph.

Proof is in the pudding.


II. Glutamine and glutamate. Biomed Pharmacother. 2002 Nov;56(9):446-57.

Tapiero H, Mathe G, Couvreur P, Tew KD.

Faculte de pharmacie, Universite de Paris, CNRS UMR 8612, 5, rue Jean-Baptiste-Clement, 94200 Chatenay-Malabry, France. haimtapiero@aol.com

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton.

---> Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue.



So the next addition to our toolbox, for a temporary boost to get metabolism working correctly is:

NAC, folic acid, and alpha-ketoglutarate.

Follow the yellowbrick road....

[Siberian]

regular gluatmine or the peptides? i dont really have the money for it right now but i have wondered this and heard conflicting points of view.

[AssItch]

Cool stuff. Glutamine seems pretty cheap these days. I have ALWAYS suspected gut issues with myself. Despite use of digestive enzymes, I have always been quite unpleasant to be around when eating big. ;)

[trouble]

Another cool tool in our molecular maniupulation tool box is to use probiotics, to help heal and condition the gut.

Thats one of the important sticking points, what we call rate limiting effect, in a cascade of reactions.

Unstick the slow point - that digestive efficiency, combination of encouraging the right microbial population (and we can do that, by diet), healing the tight junction/leaky gut issue, promoting the right mix of digestive enzymes (funnily enough, directly coupled to glutamine and to intestinal mucosal tissue repair), and priming the pump with glutamine, to kick some lazy enzymes that catalyze glutamine uptake and transport, back into active expression.

This angle on gut health - its makes this discussion we're having on hardgainer physiology unique in these bodybuilding forums.

[AssItch]

Oh yeah, I want to echo Siberian's question on glutamine peptides. Lotta people swear by them as well; I wonder if they have the same effect on gut health.

Thinkin about throwing in my order to trueprotein in the next couple days here, so I'd love to hear a little more on the topic.

[trouble]

Two articles that support what I've said about gut health the role of certain factors in the pathophysiology behind IBS.

First read is a layman's level article on IBS: pretty good, although it doesn't directly mention the neurtransmitters (beta-adrenergic) that play a role in the peristaltic and inflammation issues behind IBS and IBD. We'll get to that a little later, beause its wrapped up in the CNS issues behind hardgainer physiology.

General IBS article (http://www.vrp.com/art/559.asp?c=1146435202546&k=/det/4203.asp&m=/includes/&p=no&s=0)

Next, we turn out attention to the question of use of glutamine and glutamine dipeptides, as requested.

Glutamine (http://www.findarticles.com/p/articles/mi_m0FDN/is_4_6/ai_78539420)

I'm going to directly quote from the salient portion of this article, second page:

Gastrointestinal Disease

The gastrointestinal tract is by far the greatest user of glutamine in the body, as enterocytes in the intestinal epithelium use glutamine as their principal metabolic fuel. Most of the research on glutamine and its connection to intestinal permeability has been conducted in conjunction with the use of TPN. Commercially available TPN (solutions do not contain glutamine, which can result in atrophy of the mucosa and villi of the small intestine.

Addition of glutamine to the TPN solution reverses mucosal atrophy associated with various gastrointestinal conditions.[3] Research has demonstrated glutamine-enriched TPN decreases villous atrophy, increases jejunal weight, and decreases intestinal permeability.[4,5] Trauma, infection, starvation, chemotherapy, and other stressors are all associated with a derangement of normal intestinal permeability. One potential consequence of increased intestinal permeability is microbial translocation. Bacteria, fungi, and their toxins may translocate across the mucosal barrier into the bloodstream and cause sepsis.[6]

In numerous animal studies of experimentally induced intestinal hyperpermeability, the addition of glutamine or glutamine dipeptides (stable dipeptides of glutamine with alanine or glycine) to TPN improved gut barrier function, as well as immune activity in the gut.[7] Conditions characterized by increased intestinal permeability that might benefit from glutamine supplementation include food allergies and associated conditions, Crohn's disease, ulcerative colitis, and irritable bowel syndrome.

A clinical study of ulcerative colitis patients demonstrated that feeding 30 g daily of glutamine-rich germinated barley foodstuff (GBF) for four weeks resulted in significant clinical and endoscopic improvement, independent of disease state. Disease exacerbation returned when GBF treatment was discontinued.[8] It has also been suggested that cabbage juice consumption may provide benefit to patients with gastric ulcers and gastritis, by virtue of its high glutamine content.

The gastrointestinal tract has a large number of immune cells along its length -- fibroblasts, lymphocytes, and macrophages. The ability of glutamine to nourish these immune cells may account for its positive impact on the gastrointestinal tract and immunity. Healing of surgical wounds, trauma injuries, and bums is accomplished in part by the actions of these immune cells. Their proper functioning is dependent on glutamine as a metabolic fuel for growth and proliferation.

Therefore, a depletion of intracellular glutamine can slow growth of these cells, and ultimately prolong healing.[1] A small clinical study conducted recently in Poland demonstrated glutamine-supplemented TPN rapidly improved a number of immune parameters in malnourished surgical patients with sepsis.[9] Additional clinical trials also suggest that glutamine supplementation, as well as arginine and omega-3 fatty acids, may promote restoration of normal tissue function and intestinal permeability in post-operative patients.[10,11]

(TPN is medical jargon for liquid nutritional source)

The article goes on to discuss the role of glutamine in infectious agent resistance.

You'll find quite a few IBS patients who had bad intestinal infections as children or adolescents - which may hint either dietary or genetic predisposition, or both, to glutamine uptake and conversion to glutamate.

Looks like clinical gastroenterology practices are recommending use of the arginine-glutamine dipeptide format for glutamine supplementation in IBS.

I'd recommend trying it as opposed to glutamine capsules.

[fbarraza]

Trouble,
From another thread I remember reading you wouldn't recommend glutamine as a supplement regardless of somatype.
Please clarify.
Thanks

- Fernando

[trouble]

The dipeptide doesn't bind the same as free glutamine. It can't be easily converted to glutamate. Its not the glutamine thats the problem per se, the the glutamate receptor activation we wish to minimize.

LOL, what do you think whey has in it? A shitpot of glutamine (and in some cases, its enriched with more added by helpful manufacturers).

We want some glutamine, and we prefer to use food that has it, so that its delivered in a low dispersed dose. The dipeptide serves the purpose of delivering a smaller amount (only a fraction is cleved in the gut and delivered site specifically as glutamine to intestinal cells.

Good question; I'm not trying to equivocate here. You want just enough to help restore tight junctions for intestinal mucosal cells - after excess acid and unconjugated bile acid problems are alleviated. Else, you have a tendency to abiotically convert glutamine to glutamate in what would otherwise be a neurtral or lightly acidic environment (the normal gut).

[Hoops]

You've got a space saver, so if you're planning to go into this later please just do so then.

As always what will give us the signal that glutamine is potentially a problem?

[Weilder]

So Whey is pritty high in this Glutimine, thats good to hear. Are other sources of protien high in Glutimine as well? Like Chicken Breast's and what not??

[Jackington]

Hmmm I'm confused here too now. I was under the impressions my problems were caused if only partly by glutamine... Is it something to do with me taking "L-glutamine" rather than "glutamine" or "glutamine dipeptides"

[trouble]

Problems occur when:

-you have too much glutamine, which can be converted to acetate, and then absorbed, taken up to liver, pancreas and brain, where its readily converted to glutamate. Excess glutamate and insufficient GABA promote: insulin release, altered nitrogen balance in liver, and from excess insulin, problems with both glucose amd cholesterol regulation in muscle and liver. Oh oh.

-the local pH favors conversion of glutamine to glutamate, which stimulates cAMP, and that causes gut inflammation in intestintal mucosa.

- you have a (possibly pathogenic) community of fermentation bacteria that, when presented with an excess of glutamate, crank out acetate. This, pardon my French, fucks with calcium transport.

THIS IS WHY MANY OF US ARE CALCIUM SUPPLEMENT SENSITIVE.

You want just enough glutamine, and you do NOT want it when you have an excess of glucogenic amino acids (like you have in glutamine enriched whey products, eggs, and soy protein powders). Glutamine is important as a gene regulator of mucosal cell health. Too much, especially if you have GERD and excess bile or stomach acid, OR too much CNS stimulation of the intestines, is not a good idea.

Does this make sense?

[Khryz]

So then supplementing with GABA will help improve the ratio to glutamine levels right -- just incase you take too much?

[trouble]

I'd rather not see hardgainers taking any glutamine supplementally, other than in whey (again, not whey supplemented with extra glutamine).

Any of you can elect to take it; I just don't recommend it, due its unusual influence in excitatory chemistry in the brain, in the stomach, in the intestintal tract (ilieum and colon) and pancreas (for the skinny fat types).

[qwerty]

Trouble, sorry if this sounds like a noob question, but I've read around and some say that taking glutamine with creatine would cancel each other out, but others say that they good together just fine. So whats the real answer ??

Thx.

[DragonRider]

Next tool in our hardgainers tool box: glutamine.

This is space saver, but it basically goes like this:


the intenstines of hardgainers, the worrying type, are leaky, and thus don't have what we call tight junctions, what makes them acid and water tight.

You want these cell eges to touch and form a seal against the gut lumen contents..so that uptake is regulated by flux rate (absorption and uptake across the xell membrane.

What controls that?

Glutamine.

To read why, drop down to the studies section, my post tonight on muscle cell protein and collagen formation.

They're linked, and the turn of collagen is probably not very good in hardgainers.

At least, in the nervous phenotype.

I'll talk more about this in the next thread.

I'd rather not see hardgainers taking any glutamine supplementally, other than in whey (again, not whey supplemented with extra glutamine).

Any of you can elect to take it; I just don't recommend it, due its unusual influence in excitatory chemistry in the brain, in the stomach, in the intestintal tract (ilieum and colon) and pancreas (for the skinny fat types).

Now I'm confused. In the first post you say it is precisely for hardgainers and in post 16 you say hardgainers should not use it.


HELP.