L-Citrulline is arguably the best pre-workout supplement on the planet due to its incredible nitric oxide boosting abilities which means increased blood flow, pump and endurance.
In this article we are going to take a close look at the science backed human case studies so you can see if it’s right for you.
What is L-Citrulline
L-Citrulline is a non-essential amino acid and is found in large quantity of water melon. Your kidneys actually convert l-citrulline into another amino acid called l-arginine as well as nitric oxide via the l-arginine conversion.
L-Citrulline is commonly taken by athletes and bodybuilders because of its outstanding ability to increase nitric oxide and blood flow.
You might be wondering why not supplement directly with L-Arginine to increase nitric oxide?
L-Arginine is not effective because the body cannot convert it into nitric oxide since the liver contains high levels of the cytosolic enzyme arginase I, which breaks down arginine into urea and ornithine. (1)
With that said, a specially formulated version of L-Arginine known as nitrosigine has shown great results in clinical studies. The research is clear that supplementing with pure L-Arginine is a waste of money though. (2)
Pre-Workout Benefits of L-Citrulline
Increases Nitric Oxide & Blood Flow
Multiple case studies have proven l-citrulline to be highly effective at increasing nitric oxide production. (3, 4, 5, 6, 7)
Nitric Oxide is one of the most important molecules for blood vessel health as it’s an extremely powerful vasodilator. Vasodilation relaxes the lining of your blood vessels which causes them to widen thus increasing blood flow.
You have probably heard Arnold Schwarzenegger talk about “muscle pump” which is achieved by increasing blood flow to your muscles. Increasing nitric oxide production can help take your pump to a whole new level.
In addition to that, increasing blood flow helps speed nutrients throughout your body which provides many other benefits such as increased endurance and recovery rates which we will talk about in more depth in this article.
Increases Endurance & Training Capacity
L-Citrulline is one of the most popular pre-workout supplements for good reason. Whether you are an endurance athlete trying to increase your time trials or looking to pump out a few extra sets and reps, it can help you perform better.
Case Study 1 – Weight Lifting Volume
In a double blind human case study, researchers discovered that subjects who consumed 8 grams of l-citrulline malate were able to perform 52.92% more high intensity repetitions than their counterparts who received a placebo. (8)
Case Study 2 – Endurance Time Trials
In a double blind crossover study on healthy trained male cyclists, researchers found that l-citrulline supplementation resulted in a 1.5% time trial completion time. (9)
Case Study 3 – Vascularity, Blood Flow and Performance
Researchers concluded that l-citrulline supplementation improved skeletal muscle oxygenation, improved performance during endurance exercise and improved vascularity or blood flow and muscle pump. (10)
Case Study 4 – Decrease Blood Lactate Levels & Fatigue
When you feel that burn in your muscles when doing high intensity exercise, that is lactate build up which is basically acid in your muscles.
There are a few factors at play in regards to your bodies ability to effectively flush lactate out thereby enabling you to push harder but one of the key factors is skeletal muscle oxygen levels.
Researchers wanted to know if l-citrulline malate could help the body handle lactate build up more effectively so 4 days a week for 4 weeks, active handball players were put through an intense training regimen to improve pre-season strength.
The participants were split into two groups; one group received 3 grams of l-citrulline malate each day and the other group received a placebo.
Researchers found an incredible 60.7% decrease in blood lactate levels in the group supplementing with l-citrulline malate! (11)
In the weight lifting study I mentioned above, researchers found that participants supplementing with 8 grams of l-citrulline malate had 40% less pectoral soreness 24 and 48 hours after bench press training. (8)
In the time trial study mentioned above, the cyclists reported feeling significantly less muscle fatigue immediately following exercise. (9)
Growing muscle requires putting your muscles through significant time under tension and pushing your body to physical exhaustion.
The amount of sets and reps you can do before reaching your exhaustion limit will have a big impact on your ability to grow.
Consider case study 1 above where participants were able to perform 52.92% more high intensity repetitions and imagine how that would translate to your hypertrophy.
Ok, this really isn’t a pre-workout benefit BUT as a side benefit for many men, because l-citrulline improves nitric oxide and blood flow it also supports stronger erections and has even been used to treat men with mild ED symptoms. (12)
Increases Human Growth Hormone HGH
Research recently published in the European Journal of Applied Physiology noted that supplementing with l-citrulline malate pre-workout saw a bigger increase in HGH after intense exercise vs their placebo counterparts. (13)
Increases BCAA Utilization
In that same study, researchers found that the participants taking l-citrulline malate saw an improvement in amino acid utilization, especially branch chain amino acids (BCAA) which are crucial to increasing muscle size and strength. (13)
Side note: I recommend getting your BCAAs from whole food sources or whey protein rather than a BCAA supplement. Read more on BCAAs here to find out why.
More Powerful When Combined with Nitrosigine Arginine
L-Citrulline Malate combined with L-Arginine supplementation has been shown to increase athletic performance and decrease perceived post exercise soreness better than supplementing with either on their own. (14)
However, pure arginine is very poorly absorbed by the body so the best way to combine them is with Nitrosigine Arginine which is a highly bioavailable form of L-Arginine.
L-Citrulline vs L-Citrulline Malate (2:1)
Historically there have been two divided camps with one side claiming pure l-citrulline is best and the other saying it’s better when combined with malate in a 2:1 ratio, meaning 2 grams of citrulline for every 1 gram of malate.
So which is better?
Malate is a natural substance found in many fruits like apples and is a crucial component the tricarboxylic (or TCA) cycle which helps your body produce energy. When you increase your malate levels you increase your energy levels.
Some people have correctly pointed out that malate costs less to produce than l-citrulline and thereby assume when you add malate you are just cutting the cost of the product.
It is true malate costs less than citrulline to produce, however, this only means you need to take a higher dose of l-citrulline malate (2:1) to ensure you are getting the proper amount.
l-citrulline malate also has more human case studies showing it’s overall effectiveness for athletic performance, however, this could be simply because more studies have been done including the malate.
With all that said, either version should have a pretty equal chance of working great for you as long as you are taking the correct dosage of l-citrulline!
Side Note: We have found the Malate when mixed with other ingredients can cause extreme clumpiness once humidity touches it so pure l-citrulline may be the better choice in a bulk homemade or purchased formulation.
Dosing – How Much L-Citrulline Should You Take?
Studies suggest that if you are supplementing with L-Citrulline Malate (2:1), you take between 6 – 8 grams pre-workout. 8g would yield just over 4.5g of citrulline and approximately 3.5g malate.
If you are supplementing with pure L-Citrulline you should take 3 – 5 grams.
L-Citrulline is extremely well tolerated by most people and reported side effects are very rare.
The most commonly reported side effect is mildly upset stomach and it is often recommended to start with a lower dose and work your way up over a week or two into the higher dose ranges.
Most people who experience a mildly upset stomach will see it subside after a few doses as the body seems to adapt well.
However, you should consult with your doctor if you are taking nitrates for heart disease or ED medication such as viagra. If you are on any prescription medicine it is always best practice to check with your doctor before beginning any new supplement regime though.
- In Vivo Whole Body and Organ Arginine Metabolism During Endotoxemia (Sepsis) Is Dependent on Mouse Strain and Gender. Y. C. Luiking, M. M. Hallemeesch, Y.L.J. Vissers, W. H. Lamers, N.E.P. Deutz – Link
- Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects. T. S. Alvares, C. A. Conte-Junior, V. M. F. Paschoalin – Link
- Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Ochiai M, Hayashi T, Morita M, Ina K, Maeda M, Watanabe F, Morishita K. – Link
- L-citrulline production from L-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen. N.S. Kwon, C.F. Nathan, C. Gilker, O.W. Griffith, D.E. Matthews, D.J. Stuehr – Link
- Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise A. Sureda, A. Córdova, M.D. Ferrer, P. Tauler, G. Pérez, J.A. Tur & A. Pons – Link
- Endothelial nitric oxide production is tightly coupled to the citrulline–NO cycle. B.R.Flam, D.C. Eichler, L.P. Solomonson – Link
- Pharmacokinetic and pharmacodynamic properties of oral L‐citrulline and L‐arginine: impact on nitric oxide metabolism. E. Schwedhelm, R. Maas, R. Freese, D. Jung, Z. Lukacs, A. Jambrecina, W. Spickler, F. Schulze, R.H. Böger – Link
- Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J. Pérez-Guisado, P.M. Jakeman – Link
- Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. T. Suzuki, M. Morita, Y. Kobayashi & A. Kamimura – Link
- Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance. A. Figueroa, A. Wong, S.J. Jaime, J.U. Gonzales JU – Link
- The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise. F. Kiyici, H. Eroğlu, N.F. Kishali, G. Burmaoglu – Link
- Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. L. Cormio, M. De Siati, F. Lorusso, O. Selvaggio, L. Mirabella, F. Sanguedolce, G. Carrieri – Link
- L-citrulline-malate influence over branched chain amino acid utilization during exercise. A. Sureda, A. Córdova, M.D. Ferrer, G. Pérez, J.A. Tur, A. Pons – Link
- A combination of oral l-citrulline and l-arginine improved 10-min full-power cycling test performance in male collegiate soccer players: a randomized crossover trial. Izumi Suzuki, Keishoku Sakuraba, Takumi Horiike, Takafumi Kishi, Junya Yabe, Takashi Suzuki, Masahiko Morita, Akihito Nishimura, and Yoshio Suzuki. Eur J Appl Physiol. 2019; 119(5): 1075–1084. Published online 2019 Feb 16. – Link