Nitric Oxide (NO) Supplements: Citrulline Review - Bodybuilding Supplements

Nitric Oxide (NO) Supplements: Citrulline Review

Ever looked at the list of ingredients for your favorite NO (nitric oxide) supplement? The chances are good that—in addition to the usual arginine compounds—you’ll see citrulline listed there too. NO supplements have gotten more sophisticated in the last few years, and the addition of citrulline represents an improvement over formulas that rely on arginine alone.

Here’s the “Quick and Dirty” low down on Citrulline (click each point for more details):


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What is Citrulline?

Citrulline is a non-essential, non-protein amino acid that serves as an intermediate in the urea cycle. The urea cycle is used by the body to detoxify and excrete excess ammonia produced when amino acids are broken down. Without the urea cycle, ammonia would rapidly build up to a toxic—and ultimately fatal—level.

Other amino acids participating in the urea cycle are ornithine and arginine.

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What Does it Do?

Citrulline converts to arginine in the urea cycle, so at first glance, it would seem that they’re interchangeable. This isn’t quite true from your body’s perspective, however. Research has shown that chronic supplementation with arginine leads to increased arginase expression, which, in turn, increases the rate at which ingested arginine is broken down.

Citrulline, on the other hand, does not have this effect. On the flip side, nitric oxide synthase (NOS) regenerates citrulline in the course of converting arginine to nitric oxide. This cycling results in a much longer half life for citrulline, and ultimately, arginine in the body.

In other words, citrulline may be a better source of supplemental arginine than arginine itself.

When taken together, arginine and citrulline work synergistically to enhance NO production and improve blood flow.

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What about Therapeutic Uses?

Citrulline may prove to be useful for therapeutic purposes.

It is currently being tested in clinical trials for prevention of of hepatic venoocclusive disease (HVOD) and acute lung injury (ALI) in patients receiving chemotherapy for bone marrow transplants. A second clinical trial is also underway to see if citrulline can improve exercise tolerance in patients with Peripheral Arterial Disease (PAD).

Experimentally, citrulline has been used to prevent post-operative hypertension (high blood pressure) and to retard the progression of atherosclerosis. It appears to be quite safe, and is well-tolerated in doses up to 15 g (at least over the short term).

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Additional Exercise Performance Related Benefits

Does citrulline supplementation have any advantages for healthy, exercising people—beyond being a source of arginine for NO production?

It looks like the answer is yes, at least for the most common supplemental form, citrulline malate. During intense exercise, there are increases in both ammonia (from amino acid catabolism) and lactic acid production.

Citrulline malate can enhance the clearance of both. In addition, it’s been shown to promote aerobic energy production in exercising muscle.

There is also some experimental evidence that it can promote resistance to muscle fatigue, although (of course) more research in humans needs to be done.

It may be that the malate part of the supplement is responsible for some of these effects. A recent study looking at the effects of free form L-citrulline on exercise in healthy people actually found it reduced the time to exhaustion on a treadmill test.

Malic acid is an important metabolite in the Krebs Cycle, which is the primary metabolic pathway used by the body to produce energy. Thus, it’s entirely possible that it makes a significant contribution.

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User Comments and Feedback

The feedback on citrulline malate I’ve seen is pretty positive…not so much for strength, but for cardio. Most users report that it reduces fatigue and helps provide a boost in energy/stamina. Unfortunately, this is all anecdotal—there is very little research on the use of citrulline malate in healthy people. So it could be an example of the placebo effect in action too. I tend to doubt it, though, as some of the feedback has come from people I know who are fairly skeptical.

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What’s an useful dose?

When using bulk citrulline malate, most people use 3–6 grams, taken prior to a cardio workout. This is almost certainly a higher dose than is found in NO supplements, where it has a more supportive function.

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Citrulline Bottom Line

Overall, citrulline appears to be a promising supplement for enhancing NO production and—in the malate form—increasing endurance/stamina during aerobic exercise. As such, it’s worth experimenting with, although the bulk powder form may be preferable to a branded supplement which includes it as part of a proprietary blend.

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Recommended Products

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Your Feedback and Comments?

Have you used Citrulline? Care to share your comments? We’d love to hear from you and so would our viewers. Drop ’em into the fields below! Thanks!

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Author: elissa

Elissa is a former research associate with the University of California at Davis, and the author/co-author of over a dozen articles published in scientific journals. Currently a freelance writer and researcher, Elissa brings her multidisciplinary education and training to her writing on nutrition and supplements.


  1. While Citrulline-malate sounds like it supports Aerobic energy creation, the fact that you get tired quicker doesn’t seem like a good thing, does it?

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  2. a few seconds ago
    Hi guys…
    does anyone know how long l citrulline would last in your system…how long its effective for till its flushed out??

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    • According to the Natural Medicines Comprehensive Database:

      “L-citrulline levels are increased 10-fold after a 2 gram dose, and 100-fold after a 15 gram dose, but return to baseline within 5 to 8 hours after the dose (16470).”

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  3. I have been using Citrulline Malate (2 – 3 grams of powder in water per serve) both ‘pre’ and ‘intra’ workout for 400m sprint training since Feb 2016 and the effect has been amazing. It allowed me to do 1-2 extra hard training reps WITHOUT FATIGUE. At first I thought it must have been due to my improved fitness level so, to make sure, I tried training without it on a few occasions and noticed on each of those occasions, a more rapid drop off in energy and less capacity to do those extra reps. Considering that Citrulline helps remove ammonia and Malate is involved in energy production via the Krebs cycle, it does makes sense.

    Either way, I’m so glad I heard about it and will continue to use it
    knowing it is both safe and legal to use. The only trap is that, due to a
    tendency of mine to overtrain (and take longer to recover due to muscle
    stiffness and joint inflammation) it takes real discipline to not get carried
    away with the extra endurance and energy it provides.

    Highly recommended for intensity & strength training with an endurance

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  4. Very nice article! Thanks for the info! I first heard about Citrulline so I decided to start taking it so if you can recommend some best products that would really help!

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