Key Takeaways

  1. L-glutamine is the most prominent amino acid in the human body with exceptionally high levels in the liver, intestines, and skeletal muscle. It’s even used as a fuel source by many cells.
  2. The most common usage of L-glutamine to increase muscle growth is an outright failure.
  3. It’s a safe, cheap, and even tasty amino acid to consider experimenting with for gut health but it’s nothing impressive from a physical performance perspective.

Every now and then, companies get too invested in a product.

You find something, it looks amazing, and you name an entire product line after it. All goes well until a decade or two passes and subsequent scientific evidence gets published showing it to be rather ineffective.

It would be best to remove it from your products at this point in my opinion.

However, the more popular a supplement is (effective or not) the more scientific data is published on it. More of a “public health concern” when it’s more popular.

And sometimes, as an accidental side-effect of keeping the ineffective in dietary supplements, we learn of some other effects that it might have to warrant it staying in the product.

Or it could just remain useless. Oh science, you so silly and unpredictable!

So, what about L-glutamine?

We know for a fact that it had a bump a decade or so ago where it was “proven useless” but has recent evidence exonerated it, or is it still useless?

Let’s delve into it.

What Is L-Glutamine?

L-glutamine is the most prominent amino acid in the human body. A very versatile and important little bugger.

Not only is it highly prominent and in high levels in skeletal muscle tissue but it’s simple structure also makes it ideal as an energy source. Not for you, specifically, but while most cells in our bodies use glucose for energy, some rapidly dividing ones like immune and intestinal cells can also eat L-glutamine.

No individual amino acid can ever replace sugar but, hey, L-glutamine is trying!

Beyond that, L-glutamine is also used to create both glutamate and GABA, two neurotransmitters that form an upper/downer yin-yang balance in the brain, and due to increasing bicarbonate it can also help buffer acidity in the blood.

So ultimately, L-glutamine is an amino acid with a wide variety of roles in the body and numerous ways it could be argued to be a health supporting supplement.

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Why Do People Supplement with L-Glutamine?

l glutamine

L-glutamine supplementation tends to focus almost exclusively around muscle tissue (and exercise performance in general) as well as the intestines and liver.

These three organs comprise not only the major storage sites of L-glutamine in the body but are also areas where L-glutamine is utilized the most, which makes sense. If you have a warehouse for something it would be practical to put the manufacturing plant close by if you can.

This also includes the immune system which, due to Peyer’s patches (clusters of immune cells that are in the intestinal tract) is pretty heavily localized in the gut and partially explains the link between digestive health and immunity.

Anywho, without rambling on too much we see L-glutamine supplemented for the following reasons:

  1. Supporting gut health and alleviating symptoms from gut ailments (e.g. Crohn’s)
  2. Supporting muscle growth
  3. Promoting physical endurance

With less popular reasons to supplement L-glutamine being:

  1. Controlling carbohydrate cravings
  2. Supporting weight loss and metabolic rate
  3. Limiting anxiety and depression
  4. Serving as an antioxidant

Similar to how L-glutamine is stored in high amounts in the intestines and muscles yet is implicated almost everywhere, L-glutamine supplementation is mostly recommended for gut and muscular health with various other claims.

So let’s dig into the above and see which are valid reasons to supplement, which are hearsay, and which fall into the grey area in between.

What Are the Benefits of L-Glutamine?

The benefits of L-glutamine supplementation are rather limited, at least ones that an otherwise healthy person can put their faith into.

The rules of the game change for some topics, like when it comes to trauma, which we’ll get into in their respective sections.

L-Glutamine and Intestinal Health

The benefits of L-glutamine to the gut are pretty simple.

L-glutamine is stored in high amounts in the intestines, the intestines have adapted to this and expect high levels of L-glutamine and thus use it to repair themselves. So, when there’s an unexpected decrease in L-glutamine the intestines are less capable of repairing themselves.

The intestines get damaged regularly, to the point where they quite literally slough off their outer layers under healthy conditions. Given how frequently your intestinal cells seppuku for the sake of your body they really value their regeneration.

So when they can’t, problems arise.

And when these problems arise, giving your intestines more food to help them repair themselves helps them greatly.

This extends to conditions where the subject has an inflammatory bowel condition such as Crohn’s or Ulcerative Colitis while also applying to any condition where the gut can otherwise be damaged like in HIV (a condition where leaky gut-like symptoms can occur even without diarrhea).

Also note that this is not an amazing benefit, some studies using upwards of 21 grams of L-glutamine have failed to find benefit (Crohn’s). So a push in the right direction, not a cure.

Finally, when it comes to clinical settings where the therapy adversely affects the gut (such as chemotherapy) L-glutamine administration seems to help alleviate distress.

L-glutamine holds a lot of benefit in clinical settings for alleviating gastrointestinal distress, and for people who have some manner of inflammatory bowel condition it can also provide a good deal of relief.

L-Glutamine and Endurance Exercise

l-glutamine exercise

Glutamine seems to have a minor benefit to sub-maximal exercise performance.

How glutamine works in this case seems to be somewhat similar to L-ornithine in the sense that it helps “clean” up the blood from waste products. Reported twice to reduce ammonia build-up after an hour or so and once being reported to hinder catabolic (muscle breakdown) signaling with the more water soluble, and better absorbed, L-alanyl glutamine.

When taken in doses in the range of 70 to 100 mg/kg bodyweight, L-glutamine seems to enhance exercise that is either long in duration (lasting more than an hour) and can potentially preserve performance during sports like a basketball game.

It isn’t a major benefit, but it’s there.

L-glutamine supplementation seems to have a minor performance enhancing role similar to that of L-ornithine. Help the body clean up the blood a little bit so you can push a little harder.

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What Does L-Glutamine Not Help With?

Generally speaking, when L-glutamine fails it fails because we have more than enough of it in our bodies.

So when we, for some reason or other, suddenly deplete our L-glutamine stores a new world of benefits can open. It’s important to note that benefits that occur during trauma do not apply to otherwise healthy and well people.

Other times, well, you get the standard “people making stuff up because they can” claims associated with supplements.

L-Glutamine and Muscle Growth

The most common reason L-glutamine was, and maybe still is, supplemented is for the idea that supplementing L-glutamine will enhance muscular growth.

This idea is based off of clinical trials of L-glutamine usage in burn victims where administration (either intravenous or oral) is able to mitigate the drastic rate of muscle loss seen during third degree burns. Either that, or based off the idea that “lol, muscle has L-glutamine in it so eat more.”

Regardless of the initial claims, it simply does not work in people who haven’t been severely wounded or are otherwise highly deficient in L-glutamine.

It does work in burn victims though, and it’s damn good for them and other trauma.

This is because L-glutamine is very tightly regulated in the body and, when taken orally, will be stored in the intestines and liver. It can also be stored in the muscle both as muscle tissue or free floating. It is stored for emergency purposes, like getting burned, where it then repairs damage.

But once the storage is topped up then the simple provision of more L-glutamine isn’t going to make the body create more muscle tissue to enhance storage further. No, it’s just going to see that it’s fine on this front and let your intestines and kidneys deal with the excess.

The human diet, even a vegetarian one if protein requirements are hit, are more than sufficient for supporting L-glutamine stores in the body.

L-glutamine supplementation provides no additional muscle-building effect when given in addition to a healthy diet in metabolically healthy people. Good for people who suffered third degree burns though.

L-Glutamine and Anxiety and Depression

The link between supplemental L-glutamine and neurological ailments such as anxiety and depression is likely related to glutamate.

Glutamate, a major neurotransmitter in the body, is made from L-glutamine and is generally seen as a stimulating neurotransmitter. I say “generally” since by signaling through one of its receptors, NMDA, it can also exert potent antidepressive effects.

While many antidepressants and anxiolytics (anxiety reducers) work hand in hand, glutamate is different. In fact, excessive glutamate signaling could worsen anxiety which is sometimes seen during hangovers from alcohol (in what is called “glutamate rebound”).

But this is all irrelevant since, if it were to be a concern with supplementation, we have to first assume that oral L-glutamine goes from the gut into the brain and sufficiently influences glutamate levels.

There is absolutely no evidence of this claim and all preliminary evidence looking at this topic suggests otherwise. Glutamate is simply too vital and important a neurotransmitter to get influenced by a common dietary amino acid like this.

The rules do change for instances of protein deficiency, or course, but I don’t think I’m writing this article for Kwashiorkor-stricken third world children.

It is obscenely unlikely that oral supplementation of L-glutamine, in an otherwise fed and healthy person, will be able to influence glutamate signaling in the brain and thereafter influence anxiety or depression.

L-Glutamine and Weight Loss

l glutamine weight loss

For those of you who have heard of L-glutamine for quite some time, the idea that it can help promote weight loss may seem rather absurd.

I assure you it makes sense. Not valid scientific sense, and not overly reasonable, but it makes a wee bit of sense.

It’s possible that the reason people claim that L-glutamine causes weight loss is due to this study where supplementation caused a beneficial change in gut bacteria in overweight and obese adults.

When we say “beneficial change” in this regard, we mean a shift from one bacterial species (firmicutes) to another (bacteroidetes) that is seen during weight loss. So we got a proxy marker for weight loss here.

But it’s not like the study itself reported weight loss.

In fact, the only study I could find showing beneficial changes in body composition that wasn’t conducted in burn victims (where muscle building was a thing) was a combination study of L-glutamine and fish oil in people with chronic heart failure.

There is no current evidence to demonstrate a beneficial effect of L-glutamine supplementation on weight loss in otherwise healthy subjects. It will help people with severe burns in a clinical setting, obviously, but that’s about it right now.

L-Glutamine and Antioxidant Capacity

L-glutamine is claimed to be a potential antioxidant due to the antioxidant peptide in the human body called glutathione, which takes its namesake from glutamine.

This antioxidant enzyme, comprised of L-glutamine paired with L-cysteine and glycine, is sometimes referred to as one of the most powerful antioxidants in the human body.

Studies on L-glutamine supplementation, however, fail to find an increase in glutathione levels in otherwise healthy subjects. This may not extend to some medical conditions like Duchenne muscular dystrophy if mouse studies are anything to go by, and when used in clinical settings of trauma it can have benefit.

But just not in otherwise healthy people.

It makes sense too. Glutathione can indeed be increased in the body but the rate-limiting step, the thing that holds it back, is provision of L-cysteine. We have more than enough L-glutamine in our bodies already, we don’t need more of it to produce glutathione.

It’s only in cases where our bodies are severely damaged, and had to go through all our L-glutamine stores, that it holds benefit. Perhaps also if you are about to go into said traumatic experience, like an operation, and take glutamine beforehand as well.

If you want to increase glutathione levels as somebody who isn’t bedridden from grievous injury then consider N-acetylcysteine (NAC) supplementation which has shown benefits not only to glutathione but performance as well.

L-glutamine supplementation does not seem to hold any promise for boosting antioxidant defense in otherwise healthy people.

L-Glutamine and Carbohydrate Cravings

This one, well, it just straight up has no evidence.

The rationale behind this claim (or at least, what I can assume is the rationale) is either one of the following:

  • The fact that it’s a highly sweet amino acid means that you can put a bit of sweetness in your beverages, making a low to no carbohydrate diet more tolerable.
  • Since serotonin is known to be involved in carbohydrate preference, and serotonin is the major classical neurotransmitter in the gut that L-glutamine can help, perhaps some shenanigans are going on down there?

But it’s not like studies have been conducted to test this hypothesis.

At this moment in time there is no evidence that L-glutamine supplementation helps reduce carbohydrate cravings.

What Is the Clinically Effective Dose of L-glutamine?

It’s hard to get the “perfect” dose of L-glutamine since it’s a molecule that has requirements that will change based on your diet and the size of your skeletal muscle.

However, studies on the matter tend to use 70 to 100 mg/kg bodyweight which may be a good starting point. This translates to approximately:

  • 4.7 to 6.8 grams for a 150 lb person
  • 6.3 to 9.1 grams for a 200 lb person
  • 7.9 to 11.4 grams for a 250 lb person

It would be reasonable to say “5 grams of glutamine for those under 150 lbs and, for heavier individuals or those looking to high ball it, 10 grams.” Close enough.

Doses of up to 21 grams of L-glutamine, taken in three divided doses of 7 grams, have been used without any apparent harm.

What Types of Results Can I Expect with L-Glutamine?

l glutamine benefits

Since L-glutamine is not a rapid acting supplement for the brain there will not be any acute effects. When taking L-glutamine you may not actually feel anything from it aside from a little smile (cause, let’s be real, glutamine and glycine are both very sweet amino acids).

If you’re taking it either alone or added to a protein supplement for the purpose of inflammatory bowel conditions then, if it works, then within a week there should be beneficial symptoms occurring such as reduced bloat, gas, and pain.

But that’s pretty much it.

Does L-Glutamine Have Any Side-Effects?

L-glutamine is not known to have any major side-effects. Hell, studies on it don’t even report the “upset stomach, diarrhea, and bloating” that seems to be the standard go-to side-effect seen with pretty much any supplement.

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The Bottom Line on L-Glutamine

L-glutamine is a decent supplement.

It’s not amazing, and the increased water solubility and absorption of L-alanyl glutamine doesn’t really warrant the drastic price increase seen compared to L-glutamine itself, which is rather cheap.

If you have intestinal problems, and don’t otherwise supplement with whey protein, then it might be prudent to consider taking L-glutamine supplementation at least for a month to see how it works for you.

Don’t get your hopes up though. It’s just a step in the right direction for your gut. Nothing impressive for, like, anything else.

What’s your take on L-glutamine supplements? Have anything else to share? Let me know in the comments below!