Reading the ingredient label on any pre-workout supplement, there are a few staples you’ll consistently come across. They’re the tried and true, research-backed gems that are guaranteed to give you a solid workout.
But of those gems, there’s one that rarely gets the shining attention it deserves—L-citrulline.
If you’re looking for better performance in the gym and want to push your training volume and prevent fatigue, L-citrulline is the way to go.
It plays an important role in producing enzymes, arginine synthesis, muscle strength, and cardiovascular health, making it a staple in any of the best pre-workout supplements.
Let’s talk about all things L-citrulline pre-workout.
It’s time to chase the pump. Let’s go.
What is L-Citrulline?
Everyone loves a juicy, sweet slice of watermelon on a hot summer day, but as it turns out, chowing down on some melon pre- or post-workout could give you just the kick you’re looking for with your performance and recovery.
Not because of the sugar rush, but because it’s rich in L-citrulline, the amino acid that’s been touted for its performance-enhancing effects.
L-citrulline is a non-essential amino acid that can be synthesized in the body that’s a key component of the urea cycle in the liver and kidneys 1. But as a non-protein amino acid, it’s rarely found in food, with watermelons being one of the few sources.
However, if you’re looking to get an effective dose of L-citrulline from melon—about 3g—you’d have to eat a minimum of 7 pounds of fresh watermelon.
As with several other nitric oxide-boosting supplements, L-citrulline has gained considerable attention for its potential cardiovascular and anti-hypertensive properties, but also for its direct and indirect effects on skeletal muscle and adipose tissue metabolism 1.
But one of the main reasons we love L-citrulline in the fitness world is its conversion to L-arginine and thus nitric oxide, a potent vasodilator that enhances the delivery of oxygen and nutrients to working skeletal muscles to achieve that classic “pump” that every lifter thrives for.
What Does L-Citrulline Do In The Body?
One of the major benefits where L-citrulline is concerned has to do with nitric oxide production.
Nitric oxide (NO) is a gaseous signaling molecule that is involved in regulating a number of vital biological functions, and low levels of NO have been implicated in the development of multiple age- and lifestyle-related risk factors and diseases like hypertension, atherosclerosis, insulin resistance, type 2 diabetes (T2D), and cardiovascular disease 1.
In endothelial cells, NO is produced from its precursor amino acid, L-arginine, by endothelial-nitric oxide synthase (eNOS) to generate the production of NO and L-citrulline as byproducts.
Increasing levels of NO activates guanylate cyclase (sGC) in smooth muscle cells, which catalyzes cyclic guanosine monophosphate (cGMP) synthesis 2.
cGMP functions as an important cellular messenger and plays key roles in several biological processes, including vasodilation of blood vessels 3. With better blood flow may come better exercise performance.
That’s assuming we’re making enough nitric oxide to sustain proper levels.
Along with reduced synthesis, increased levels of reactive oxygen species (ROS) can also reduce the bioavailability of NO, which further contributes to endothelial dysfunction.
As such, supporting the production of L-arginine may be an alternative way to boost NO synthesis and bioavailability.
However, because oral L-arginine supplementation is largely ineffective and can cause GI distress, we look towards supplementing L-citrulline to directly increase plasma and tissue levels of L-arginine and thus NO bioavailability 4, 5.
Studies also suggest that nitric oxide influences Akt signaling through a cGMP/PI3K-dependent pathway, the main pathway for boosting translation initiation and protein synthesis in skeletal muscle 6.
But it also appears to influence skeletal muscle function via excitation-contraction coupling, myofibrillar function, perfusion, and metabolism.
As such, L-citrulline combined with glutathione may elicit improvements in cGMP activity, which could mean it plays an important role in muscle protein synthesis and muscle performance during resistance training protocols.
Should You Take L-Citrulline Pre-Workout?
As we’ve said, the main reason people dose up on citrulline pre-workout is to increase nitric oxide production, and L-citrulline indirectly increases NO biosynthesis by increasing L-arginine synthesis.
As a result, it may lead to improvements in endothelial vasodilator function. When blood vessels are more dilated, it not only increases cardiometabolic function but also delivers nutrients and oxygen to working muscles and enhances the removal of waste and byproducts that can contribute to muscle fatigue 7.
However, the research surrounding L-citrulline supplement alone is quite mixed, with the effects being more noticeable in untrained individuals, which suggests that you may not get the results you’re hoping for supplementing with just citrulline.
So, rather than waste your money, invest in something that will get you results. Citrulline combined with other compounds seems to offer more benefits where exercise performance is concerned.
Here’s what we recommend.
When you pair L-citrulline with glutathione and a solid resistance training program, you’re signing up for maximum performance. It’s the perfect blend of compounds to enhance nitric oxide production and sustain blood levels for a bigger and better pump throughout your entire workout.
Combined supplementation of glutathione (GSH) with L-citrulline in response to just a single bout of resistance training can increase plasma nitric oxide metabolites, nitrite and nitrate, and cyclic guanosine monophosphate (cGMP), which may play an important role in muscle protein synthesis 8.
A randomized, double-blind, placebo-controlled study of 75 resistance-trained males supplementing with GSH + L-citrulline (GSH + CIT), L-citrulline-malate, or cellulose placebo daily for eight weeks, in conjunction with eight weeks of resistance training, found that the GSH + CIT group increased lean mass after four weeks of training along with muscle strength.
Not just that, but the combination of GSH and CIT can improve and sustain levels of nitric oxide even after exercise has stopped. A similar study found that nitrate, nitric oxide, and plasma cGMP were all significantly increased in the group supplementing with L-citrulline and GSH 2, along with greater levels of nitrite and NO 30 minutes post-exercise compared to the group taking a placebo.
When it comes to getting a bigger and better pump, boosting nitric oxide levels is non-negotiable. And while several compounds can support NO, L-citrulline is a staple.
It’s been shown to be more effective than supplementing with pure L-arginine, making it a staple in our stack. What’s more, when you combine with glutathione, you’re getting maximum NO levels for a pumped-up performance in every workout.
- TD Allerton, DN Proctor, JM Stephens, TR Dugas, G Spielmann, BA Irving. l-Citrulline Supplementation: Impact on Cardiometabolic Health. 2018;10(7):921.
- S McKinley-Barnard, T Andre, M Morita, DS Willoughby. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis.J Int Soc Sports Nutr. 2015;12:27.
- SM Bode-Böger, RH Böger, A Galland, D Tsikas, JC Frö L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998;46(5):489-497.
- GK Adverse gastrointestinal effects of arginine and related amino acids.J Nutr. 2007;137(6 Suppl 2):1693S-1701S.
- E Schwedhelm, R Maas, R Freese, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.Br J Clin Pharmacol. 2008;65(1):51-59.
- JA Drenning, VA Lira, QA Soltow, et al. Endothelial nitric oxide synthase is involved in calcium-induced Akt signaling in mouse skeletal muscle. Nitric Oxide. 2009;21(3-4):192-200.
- K Takeda, M Machida, A Kohara, N Omi, T Takemasa. Effects of citrulline supplementation on fatigue and exercise performance in mice.J Nutr Sci Vitaminol (Tokyo). 2011;57(3):246-250.
- P Hwang, FE Morales Marroquín, J Gann, et al. Eight weeks of resistance training in conjunction with glutathione and L-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained males.J Int Soc Sports Nutr. 2018;15(1):30.