The Complete Guide to L-Arginine Supplementation

Ah, L-arginine. Probably one of the more important performance enhancing supplements to be released in the past two decades.

Did you know that, if we go back far enough, there was once a time where a “pre-workout” supplement didn’t exist? If you asked for a pre-workout you’d get a bagel and a coffee, nothing more and nothing less.

It was because stimulants worked. Sure you had some people sniffing ammonia caps and others taking “less than legal” stimulants but that was it. It was all about the buzz and letting that buzz carry you through your workout.

Then the pre-workout supplements came on the back of L-arginine. They proved that you could actually increase physical performance not only in a manner that wasn’t stimulatory but could be used alongside stimulants.

And that, dear readers, is when the crazy train derailed and everybody started to put everything under the sun in their pre-workouts. People started walking around at the gym not with coffees, but with shaker bottles filled with fluorescent liquids.

It was a magical time for companies, I assume, since your customers do the marketing for you when they’re killing time between sets and somebody asks why they’re drinking fizzy Kool-aid in a plastic bottle.

Since then we’ve gotten back on the rails, brought science back into the topic (honestly, it wasn’t really there from the get-go), and pre-workouts are becoming more simplified and streamlined.

What about L-arginine though? Should it have faded away with the times or does it still have a viable position in pre-workouts these days?

Table of Contents

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• What Is L-Arginine?
• Why Do People Supplement with L-Arginine?
• Does L-Arginine Work?
• L-Arginine vs. L-Citrulline
• L-Arginine vs. Agmatine
• What’s the Clinically Effective Dosage of L-Arginine
• What Types of Results Should I Expect with L-Arginine?
• Does L-Arginine Have Any Side Effects?
• What’s the Best Type of L-Arginine?
• The Bottom Line on L-Arginine

What Is L-Arginine?

L-arginine is an essential amino acid in the human diet. It’s found in pretty much any protein-containing food to a degree and, unlike lysine or L-methionine, isn’t really associated with any deficiency state in modern countries; we get plenty even with a bad diet.

It’s used in dietary supplements because of its interactions with a small molecule called nitric oxide. Quite literally a nitrogen molecule bound to oxygen, this gas exists in blood vessels for a short time where it works to improve blood flow and L-arginine increases its synthesis.

L-arginine, however, was the very first “nitric oxide booster” researched in depth and as soon as it was shown to work it was being sold in dietary supplements. Later on, it was found that other supplements did the same job either better or simply more reliably, though, which we’ll discuss in a moment.

Later research proved that, although L-arginine works, it’s not as good as other compounds for increasing nitric oxide production.

Why Do People Supplement with L-Arginine?

The main reason that people supplement L-arginine is for increasing blood flow, mostly during exercise but also for some other conditions such as cardiac damage or erectile dysfunction.

It’s the most popular blood flow enhancing supplement in part due to it’s association with pre-workouts, being the main ingredient of which the entire genre was based upon (as rationale for why it wasn’t “just a stimulant”).

Others say that L-arginine, because L-arginine increases blood flow, it also helps the body “deliver more nutrients to the muscles. That claim is unsupported and rather silly in retrospect since, if your body was unable to deliver nutrients to your muscle tissue during exercise, you’d probably plop over dead from a blood clot.

Generally, L-arginine is simply seen as a blood-flow enhancing supplement that’s also gotten mixed in with a lot of exercise-related claims due to it’s association with pre-workout supplements.

Does L-Arginine Work?

Well, the money question; does L-arginine work?

Yes, yes it does.

There are a few catches here though, and good reasons why you shouldn’t run out and buy L-arginine. L-arginine works for blood flow yet is somewhat unreliable in doing so and, even if increasing blood flow is your goal there are better options out there already.

Before we get into the better options, and why they are better options, we need a short primer on how they all work. It really boils down to two words: nitric oxide.

Nitric oxide (NO) is a small gas that, when created, relaxes blood vessels and allows blood to flow easier. It exists for a very short time before it degrades so supplementing NO itself is futile and instead we need to focus on stuff that encourages the body to make more.

L-arginine, present in food products, is literally the amino acid from which NO is made. When exposed to the enzyme called Nitric Oxide Synthase (NOS) a nitrogen is plucked from L-arginine and paired to oxygen to get NO; L-citrulline is then made as a byproduct.

L-citrulline then floats around a bit and, when it gets to the kidneys, can turn back into L-arginine to keep the cycle going.

It was thought for a long time that L-arginine followed a sort of “substrate” mentality, the idea being that the limiting factor in nitric oxide production was how much L-arginine was available for the NOS enzyme to process. The more L-arginine in your system, the more nitric oxide you can produce, or so they thought.

Thing is, this led to what was known as the L-arginine paradox in research. L-arginine turns into NO, but the NOS enzyme is already working at it’s maximum speed and shouldn’t be able to make NO faster, but L-arginine . . .  still increased NO?

For a time this made no sense, if the assembly line is maxed out then adding in more raw material should cause a backlog and not more refined product.

Then it was discovered that L-arginine actually works by stimulating the NOS enzyme, particularly the NOS variant found in blood vessels (henceforth, eNOS) by acting on another receptor called the alpha-2-adrenergic receptor.

So L-arginine basically has a dual role here; it’s the thing from which NO is made from but also tells the eNOS enzyme to get off its butt and make more NO.

It all sounds great, so why are there better options and what are they?

L-Arginine vs. L-Citrulline

As mentioned earlier, L-arginine turns into L-citrulline when it’s used up and then L-citrulline floats down to the kidneys to get turned back into L-arginine. These two amino acids, as well as L-ornithine, are major players in regulating nitrogen and ammonia in the body.

If you increase either L-arginine or L-citrulline in the blood you can expect the other one to be influenced by it. When it comes to the receptor in question as well, the A2A receptor, they’re also both equally effective since, well, L-citrulline transforms into L-arginine beforehand so they’re literally the same molecule.

So why’s L-citrulline better?

Absorption. Intestinal absorption is the reason.

When somebody puts L-arginine into their mouth the amount you absorb is all over the map. The more you take, the less you absorb, but a good average is about 70 percent at 6 grams (range of 50 to 90 percent absorption approximately) while at 10 grams it can drop to 20 percent absorption (5 to 50 percent range).

Whatever isn’t absorbed goes to the colon where it can then promote diarrhea and cramping, meaning that the more you take the greater the risk of digestive upset.

L-citrulline, however, is taken up in a more controlled manner by more transporters with the absorption rate generally being seen as “complete”; or as close to 100% as one can get. These transporters for L-citrulline even exist in the colon itself, not just the small intestines!

Bottom line, there’s a much lower chance of any L-citrulline causing diarrhea, cramping, or any other problems.

If L-citrulline isn’t absorbed, then it doesn’t carry the same diarrhea risk since it needs to get to the kidneys first to turn into L-arginine. If it ain’t absorbed then it can’t get to the kidneys, can’t turn into L-arginine, and can’t cause digestive upset.

This is why I opted for L-citrulline in PULSE rather than L-arginine. It’s just more reliable with fewer side effects. No reason to use L-arginine unless you’re trying to needlessly cut costs after all.

Ultimately, L-citrulline is just as effective as L-arginine, more reliable at causing beneficial effects, and has a lower risk of digestive side effects. This is why I included L-citrulline in our pre-workout supplement, PULSE.

PULSE also contains 5 other ingredients at clinically effective doses that are proven to enhance workout performance.

It’s also naturally sweetened and flavored and contains no artificial food dyes, fillers, or other unnecessary junk.

So, if you want to feel focused, tireless, and powerful in your workouts . . . and if you want to say goodbye to the pre-workout jitters, upset stomachs, and crashes for good . . . then you want to try PULSE today.

L-Arginine vs. Agmatine

Agmatine is a neurotransmitter derived from L-arginine. It has an astounding amount of different actions in the body, most of which are neurological, which led us to use it in our ASCEND nootropic since it is, quite frankly, great.

When it comes to the specific mechanism we’re talking about in this article however, agmatine shows promise but doesn’t have the human studies behind it yet.

It’s known to reduce blood pressure in rats when injected and doesn’t do this directly via NO (unlike L-arginine, agmatine can’t itself give off NO) but insteads acts on the aforementioned A2A receptor.

The kicker, however, is that it’s dramatically more potent. L-arginine needs a concentration of 1 millimole to activate the receptor the same degree as 10 micromole of agmatine; a 100-fold difference.

This isn’t to say that putting agmatine in your mouth is going to be 100 times as effective as L-arginine, the body likes to regulate the level of nitric oxide production and would rather not drop dead from low blood pressure if it could. But, agmatine holds promise as being able to improve blood flow more than L-arginine once human studies work out the dosages a bit.

But that’s where we stand right now, twiddling our thumbs and hoping that agmatine is a better option than L-citrulline.

Agmatine has potential to be “stronger” than L-arginine and L-citrulline when it comes to creating nitric oxide, but it’s less “clean” of a nitric oxide booster; affecting more systems overall and currently without the human studies to back up its use in pre-workouts.

What’s the Clinically Effective Dosage of L-Arginine

The clinically effective dose of L-arginine is widely thought to be, well, about six grams acutely. Even when you take an overall higher dose (throughout the day) the five to seven-ish range is the highest used in single doses.

This is mostly because studies that use three grams of L-arginine or less tend to not show many benefits (although they do at times) suggesting it’s not as much as we’d want whereas taking 10 grams or more of L-arginine is in the range where intestinal side effects occur more frequently due to poor absorption.

Six grams or so is the happy medium where side effects in the gut are still somewhat minimal yet you get more L-arginine than you would with a three gram dosage.

What Types of Results Should I Expect with L-Arginine?

If you choose to supplement L-arginine then you can expect the following:

1. Doses of around five grams before a workout have the potential to improve your performance, usually when it comes to anaerobic endurance.
2. Doses of around 10 grams or higher have the same chance to do this but may also give intestinal side effects that really “put a cramp” in your workout.
3. The efficacy of L-arginine will likely depend heavily on the state of your intestines, what food you ate beforehand, and, frankly, it’s just not reliable. Sometimes it works and sometimes it doesn’t.

You can definitely see benefits with L-arginine but it’s not something to put all your hope into.

Does L-Arginine Have Any Side Effects?

The most common side-effect of L-arginine supplementation is loose stool, or more specifically osmotic diarrhea, which means diarrhea caused by excess water and electrolytes in the intestines.

It’s also the primary reason why there’s been a shift towards L-citrulline supplementation over L-arginine supplementation.

While we normally just say that L-citrulline has better absorption from the intestines, which it does, the reason we care about this rather than just pumping up the dose of L-arginine we take is because L-arginine that isn’t absorbed from the intestines is still able to affect the intestines.

When it gets to the colon, L-arginine can indeed promote nitric oxide production. This, however, draws ions into the colon (and water then follows) that prompt diarrhea in a similar manner to how magnesium works to induce diarrhea.

Since L-citrulline is well absorbed from the intestines and, even if it isn’t, needs to get to the kidneys first to become “activated,” it doesn’t cause these problems.

Beyond that the only other major concern is when it comes to cold and herpes sores. L-arginine and lysine have an antagonistic relationship when it comes to managing viral sores and putting a bunch of L-arginine in the body can potentially make a sore flame up.

It’s medically benign, so not a major concern, but could cause some embarrassment otherwise.

Finally, it’s unlikely that L-arginine can induce symptoms of low blood pressure since not only is its mechanism well regulated (the eNOS enzyme) but it’s only moderately potent even on a good day. Dizziness and the like are unlikely.

For the most part, the only side-effects of L-arginine supplementation is a potential flare up of viral sores and diarrhea when too much is taken at once.

What’s the Best Type of L-Arginine?

L-arginine tends to be sold in the form of L-Arginine Alpha-ketoglutarate (henceforth L-Arginine AAKG) or simply as the amino acid itself without any other molecules attached to it.

There’s nothing overtly fancy with L-Arginine AAKG. It’s similar in concept to Alpha-GPC where you have the “main” thing you want and then bind it to another goodies on the basis of “well, maybe the other goodies do cool things?”

In the case of AAKG, alpha-ketoglutarate is an intermediate in the Kreb’s cycle (the cycle that produces energy in a cell) and it’s thought that providing some of these intermediates allows cells to produce a little more energy.

However, studies on L-Arginine AAKG tend to show the same stuff as L-arginine by itself. It works sometimes, and sometimes it doesn’t. The AAKG doesn’t seem to increase reliability much.

This is another reason the best form of L-arginine is, unexpectedly, L-citrulline.

The Bottom Line on L-Arginine

At the end of the day, L-arginine burst forth onto the scene and carried with it a ton of information and knowledge pertaining to nitric oxide. It should be heralded, in a way, for bringing attention to this little gas that can benefit our lives.

It’s since become old hat, though. L-citrulline is clearly the better choice, and the future promise of nitric oxide boosters seems to be focused on either stronger supplements to induce nitric oxide, such as agmatine, other ways to get nitric oxide, like dietary nitrates, or support molecules that can preserve nitric oxide like pycnogenol.

L-arginine is just boring, uneventful, and overall decent.

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