The Complete Guide to L-Citrulline Supplementation

Take a look at the best pre workout supplements on the market and you’ll notice basically all of them have a few common ingredients proven by science to significantly enhance performance, power, and lean mass. But one in particular has been gaining a lot more attention lately.   


Here’s a hint, it’s not caffeine or beta alanine or even creatine.




Ok, then we’ll help you out. The one key ingredient all of the best pre workouts contain is L-Citrulline.


This mighty amino acid is your ticket to better workouts, faster recovery, and the most powerful muscle pumps you’ve ever experienced. If you’re not familiar with this potent ergogenic, hang around, because we’ve got all the reasons why L-Citrulline is a must have ingredient in your favorite pre workout supplement!




What is Citrulline?


L-citrulline is a nonessential amino acid, meaning the body can produce all it needs and is not required to obtain it through the diet.[1] Citrulline is derived from the Latin word for watermelon (citrullus), and is found in relatively high amounts in the fruit, approximately 1.1-4.7mg/g.[2] The amino acid is also found in a number of other common foods including:


  • Cucumber

  • Melons

  • Pumpkin

  • Squash

In the body, citrulline is produced in the liver and intestines from either L-Glutamine or L-Arginine.[1] Interestingly enough, when ingested via supplementation, L-Citrulline is actually converted to L-arginine and used to enhance nitric oxide production, but more on that later.


L-citrulline plays a key role in the production of important enzymes, arginine levels, muscle strength, and cardiovascular health. How can one “nonessential” amino acid have such a profound impact in the body?


Let’s find out!

What does Citrulline do?


Following ingestion, whether through supplementation or food, citrulline is converted to arginine by the and released into the bloodstream, where it’s then put to use in the body for a number of different uses.[3,4] Perhaps the most well known of these uses for citrulline is to increase nitric oxide (NO) production. Since citrulline is converted into arginine, and L-arginine is the precursor to nitric oxide, increased consumption of citrulline results in higher nitric oxide production, and it from this that most of citrulline’s performance benefits are derived.[5]


Interestingly enough, citrulline is also formed as a byproduct of nitric oxide production. It can then be recycled back to l-arginine by way of the Citrulline-NO cycle.[6]


Aside from enhancing NO production, citrulline also plays a crucial role in the urea cycle along with arginine and ornithine. The urea cycle is responsible for converting ammonia into urea, which is then excreted from the body through urine. In case you weren’t aware, ammonia is a compound that can be extremely toxic to cells. Elevated levels of ammonia in skeletal muscles can induce fatigue, inhibit energy production, and reduce glycogen formation. If ammonia levels get too out of control, it can even cause premature cell death. But with increased citrulline levels in the body, the body’s ability to buffer this ammonia buildup is significantly enhanced leading to better stamina, endurance, and all around performance.


Citrulline also increases the rate of ATP synthesis during exercise as well as phosphocreatine (CP) recovery after exercise. An athlete’s inability to rapidly generate ATP will lead to premature fatigue and that quintessential feeling of "hitting wall" during training.




L-Citrulline vs L-Arginine


You noticed above that L-Citrulline is converted to L-Arginine which leads to greater NO production, and a number of important performance benefits, which we’ll address in a minute. But you’re probably wondering why not simply use L-arginine to increase NO production instead of a compound that must first convert to L-arginine and then nitric oxide.


Simply put, L-arginine has incredibly poor bioavailability in the body (~20%) when orally supplemented, meaning that any free form L-arginine supplement you take really won’t do much to increase blood levels of arginine. This is due to L-arginine being quickly degraded and removed from the body due to the actions of a devious little enzyme called arginase present in the gut.[7]


However, L-citrulline uses a different transporter in the gut when it is absorbed than L-arginine, which means it is not prematurely broken down and survives the tortuous journey through the digestive system and onto your intestines, where it’s then absorbed and transported into the bloodstream and subsequently converted to arginine, and from there significantly increases NO production.[8]


Theoretically, you could still take L-Arginine to increase NO production, but you’d have to use a rather large does of it (~10g). The problem is, L-Arginine has some rather nasty side effects when taken in large doses including GI distress, nausea, vomiting, and diarrhea[9], not exactly something you want to deal with right before a heavy set of squats. Citrulline, on the other hand, doesn’t have this problem when consumed at high doses.


Basically, Citrulline is a superior nitric oxide booster to arginine, and one that won’t cause any sort of stomach issues preceding your workout. Now, let’s take a look at what this powerful amino acid can do for your performance and overall health.


Benefits of Citrulline


Increases Nitric Oxide Production


The most well known benefit of L-citrulline is its ability to significantly boost NO levels in the body.[10,11]


Why is more nitric oxide a good thing?


Nitric oxide is an important cell signaling molecule that enhances vasodilation, blood flow, oxygen delivery, nutrient transport, glucose uptake, and muscle growth. Increased oxygen and nutrient delivery to working muscles allows them to resist fatigue and continue to perform at a high level, leading to more weight and reps performed and ultimately better gains. 


Greater nitric oxide production also promotes bigger, badder, and nastier muscle pumps, and if you want to learn the how and why of getting a pump can improve muscle growth, click here.


Enhances Blood Flow


A by-product of increased nitric oxide production is increased blood flow[10,11,12], and with that greater delivery of essential nutrients your mind and muscles need to function optimally and resist fatigue. Plus, increased blood flow also brings with it increased amino acid delivery to your muscles, which are used as the “building blocks” to repair and grow muscle tissue during and after intense training.


Improve Athletic Performance


Numerous studies have shown that supplementing with L-citrulline significantly enhances resistance and endurance training. One study in particular gave subjects a dose of 6g L-Citrulline and documented a 34% increase in physical output capacity and intensity.[13] This was due to an increase in cellular energy production, better known as ATP. Another study using the same 6g dose of L-Citrulline (the same dose contained in Mega Pre!) observed improved V̇o2 kinetics, tolerance to intense exercise, and exercise performance in healthy adults.[17]

Other trials using l-citrulline have noted increased exercise capacity in endurance activities (walking and cycling) and resistance training (bench press).[14,15,16]


Reduces Fatigue


Not only does L-Citrulline help you perform better for longer, it also reduces fatigue during exercise as well. Several double-blind, randomized control trials (the highest quality studies) found that consuming L-Citrulline prior to exercise reduced fatigue following intense training. L-Citrulline increased production of creatine phosphate (CP), an alternative form of energy used by muscles.[13]

Subjects using citrulline also were able to perform more reps and experienced less soreness following training.[15,16] In other words, if you’re looking to really push your limits and excel in your training, L-Citrulline is a MUST HAVE ingredient.


Decreases Blood Pressure

One of the many results of increased NO production, aside from enhanced performance, is vasodilation, widening of the blood vessels. This relaxation lowers blood pressure, both systolic and diastolic, which promotes cardiovascular health and is being explored as a treatment for heart failure.[17,18].


Supports Heart Health


The heart is a vital muscle/organ in the body that’s responsible for pumping blood to all the areas of your body that allow you to perform at a high level and essentially stay alive. It turns out L-Citrulline can also improve the function and health of your heart too!

Research conducted in patients with heart failure noted that l-citrulline improved function of the left and right ventricles as well as endothelial function.[19] Another study conducted in heart failure patients found that citrulline reduced blood pressure in the pulmonary artery and increased the volume of blood pumped out of the right ventricle.[14,20]


Boosts Immunity


Citrulline may also help you avoid getting sick too! Research on male cyclists found the consuming L-Citrulline prior to training improved the function of neutrophils, an important class of white blood cells that fight infection.on [21].


May Increase Growth Hormone


A different study conducted on cyclists found that L-Citrulline supplementation led to increased levels of human growth hormone following exercise. Growth hormone is an important anabolic hormone that promotes cell growth, cell reproduction, and cell regeneration, higher levels of this powerful hormone can lead to bigger, better muscle growth from your training.[22] Researchers believe the increase in growth hormone is due to increased arginine levels in the body, as arginine inhibits the release of Growth Hormone-Inhibiting Hormone.


May Enhance Erectile Function


Not only does L-Citrulline enhance your performance in the gym, it can also give you a much needed boost in the bedroom too! Research conducted in men age 55 and older found that supplementing with L-Citrulline improved erection hardness and symptoms of erectile dysfunction (ED).[23] On top of that, some men even reported more satisfaction from sex and having more of it too!function (ED) and increases the hardness of erections. Some men reported having more sex after treatment and being more satisfied.




Treat Urea Cycle Disorders


Being that L-Citrulline is one of the three primary amino acids needed for proper functioning of the urea cycle, it stands to reason that supplementation with the amino acid could treat disorder of the toxin removing cycle. And research backs that up too!

Studies show that supplementing with L-Citrulline enhances ammonia removal from the bloodstream as well as preventing accumulation of it.[1]




With the volumes of research that have been conducted on L-Citrulline, there have been a wide variety of doses used, each showing positive benefits for the patients involved. Doses have ranged from 1.5g per day all the way up to 6g pure L-Citrulline. The general consensus is that a minimum of 3g pure L-Citrulline is needed to begin to experience the performance enhancing benefits of the amino acid, and when dosed at 6g, that’s where significant improvements in performance and recovery really start to become evident.


That’s why Primeval Labs has included a full 6g dose of L-Citrulline in each serving of Mega Pre.


Any Side Effects?


Citrulline is fairly safe for most people to use, the only minor side effect that has been reported on occasion is some minor GI upset, though nowhere near the extent of arginine.[15,18].


L-Citrulline vs Citrulline Malate


Very frequently, you’ll see supplements using Citrulline Malate as opposed to L-Citrulline and you might be wondering if one is better than the other. Citrulline Malate is a combination of l-citrulline and malic acid (malate). The difference being that you get about half the dose of citrulline with citrulline malate compared to pure l-citrulline.


For example, if you have 6g citrulline malate, you’re only getting around 3g l-citrulline, with the other 3g being malic acid. However, when using pure L-Citrulline, you get the full 6g, and all the performance enhancing benefits with it.


Simply put, if you’re using citrulline malate, you’re going to have to use A LOT more of it to get the same yield of citrulline from the same amount of pure l-citrulline.


Experience the Power of Citrulline with Mega Pre


L-Citrulline is an incredibly powerful supplement, and one every athlete should be using whether you’re playing in the pros or just lifting a few times per week at the local gym. Increased performance, less fatigue, and greater growth, you get it all with L-Citrulline.


Primeval Labs Mega Pre includes a whopping 6g pure L-Citrulline in each serving to give you significantly better NO production, blood flow, performance, and best of all, MASSIVE MUSCLE PUMPS. Try a serving for yourself today, and experience first hand all the benefits L-Citrulline has to offer.






  1. Oketch-Rabah HA, Roe AL, Gurley BJ, Griffiths JC, Giancaspro GI. The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline. J Nutr. 2016;146(12):2643S-2651S. doi:10.3945/jn.115.227280.

  2. Kobayashi Y, Narita K, Chiba K, Takemoto H, Morita M, Morishita K. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice. Pharmacognosy Research. 2014;6(4):297-302. doi:10.4103/0974-8490.138269.

  3. Eberhardt D, Jensen JVK, Wendisch VF. L-citrulline production by metabolically engineered Corynebacterium glutamicum from glucose and alternative carbon sources. AMB Express. 2014;4:85. doi:10.1186/s13568-014-0085-0.

  4. Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005;29(3):177-205. doi:10.1007/s00726-005-0235-4.

  5. National Center for Biotechnology Information. PubChem Compound Database; CID=9750,  

  6. Mori M, Gotoh T. Regulation of nitric oxide production by arginine metabolic enzymes. Biochem Biophys Res Commun. 2000;275(3):715-719. doi:10.1006/bbrc.2000.3169.

  7. Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral l-arginine in normal volunteers. British Journal of Clinical Pharmacology. 1999;47(3):261-266. doi:10.1046/j.1365-2125.1999.00883.x.

  8. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology. 2008;65(1):51-59. doi:10.1111/j.1365-2125.2007.02990.x.

  9. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr. 2007;137(6 Suppl 2):1693S-1701S.

  10. Ochiai M, Hayashi T, Morita M, et al. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol. 2012;155(2):257-261. doi:10.1016/j.ijcard.2010.10.004.

  11. El-Hattab AW, Emrick LT, Hsu JW, et al. Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation. Molecular genetics and metabolism. 2016;117(4):407-412. doi:10.1016/j.ymgme.2016.01.010.

  12. Seddon M, Melikian N, Dworakowski R, et al. Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo. Circulation. 2009;119(20):2656-2662. doi:10.1161/CIRCULATIONAHA.108.822205.

  13. Bendahan D, Mattei J, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone P. Citrulline/malate promotes aerobic energy production in human exercising muscle. British Journal of Sports Medicine. 2002;36(4):282-289. doi:10.1136/bjsm.36.4.282.

  14. Orozco-Gutierrez JJ, Castillo-Martinez L, Orea-Tejeda A, et al. Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. Cardiol J. 2010;17(6):612-618.

  15. Perez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J strength Cond Res. 2010;24(5):1215-1222. doi:10.1519/JSC.0b013e3181cb28e0.

  16. Suzuki T, Morita M, Kobayashi Y, Kamimura A. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. Journal of the International Society of Sports Nutrition. 2016;13:6. doi:10.1186/s12970-016-0117-z.

  17. Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM. l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol. 2015;119(4):385-395. doi:10.1152/japplphysiol.00192.2014.

  18. Alsop P, Hauton D. Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure. European Journal of Applied Physiology. 2016;116:1651-1661. doi:10.1007/s00421-016-3418-7.

  19. Balderas-Munoz K, Castillo-Martinez L, Orea-Tejeda A, et al. Improvement of ventricular function in systolic heart failure patients with oral  L-citrulline supplementation. Cardiol J. 2012;19(6):612-617.

  20. Orea-Tejeda A, Orozco-Gutierrez JJ, Castillo-Martinez L, et al. The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction. Cardiol J. 2010;17(5):464-470.

  21. Sureda A, Cordova A, Ferrer MD, et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009;43(9):828-835. doi:10.1080/10715760903071664.

  22. Sureda A, Cordova A, Ferrer MD, Perez G, Tur JA, Pons A. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010;110(2):341-351. doi:10.1007/s00421-010-1509-4.

  23. Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011;77(1):119-122. doi:10.1016/j.urology.2010.08.028.