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Written by Michael J. Rudolph, Ph.D.
05 December 2018

16NN276-Cit

Which is the Best NO2 Booster - Citrulline vs. Arginine

 

 

The signaling molecule nitric oxide (NO), made up of one nitrogen atom and one oxygen atom, has become a popular compound in the weightlifter’s arsenal for greater exercise performance. NO has many roles, but the one athletes desire most is increased blood flow caused by vasodilation that occurs when NO activates several cellular signaling cascades that relax the smooth muscle within the arterial wall, causing the arteries to dilate or open up. Greater vasodilation within the arterial wall generates increased blood flow, bringing more essential nutrients and oxygen to laboring muscles while simultaneously removing metabolic waste— which collectively enhances muscular performance.

Since NO is biosynthesized from the amino acid arginine, increased consumption of arginine should noticeably boost arginine levels in the blood, driving greater production of NO. However, arginine is poorly absorbed by the intestine1 and is quickly broken down by the liver,2 significantly reducing its bioavailability and capacity to increase NO production. On the other hand, the amino acid citrulline, which is quickly converted in the body into arginine, is effectively absorbed by the intestines and avoids breakdown by the liver.3 Consequently, citrulline consumption represents a unique way to vigorously increase endogenous arginine levels and drive NO production for considerably improved muscular endurance and strength.

 

Citrulline More Potently Increases NO Production

While arginine consumption is the more logical choice to increase arginine levels within the body, its lack of bioavailability makes it an inferior choice compared to the much more absorbable citrulline. Greater citrulline absorption into the body actually supports superior levels of arginine biosynthesis. This somewhat counterintuitive outcome was clearly demonstrated in a study by Osowska et al.4 that found citrulline consumption produced a substantially larger amount of arginine in the blood and muscle tissue when compared to either arginine or placebo ingestion. Furthermore, another study by Schwedhelm et al.5 showed that citrulline's capacity to yield more endogenous arginine also triggered increased NO production and NO-dependent signaling. While greater NO production and signaling due to citrulline is remarkable, it is even more notable that citrulline supplementation was shown6, in children undergoing surgical procedures for congenital heart lesions, to steadily increase plasma arginine levels and NO production— which reduced the risk for postoperative hypertension, indicating better cardiovascular performance as a result of improved vasodilation triggered by NO. Collectively, these studies confirm that supplementing the diet with citrulline is more effective than arginine for boosting endogenous arginine levels. Moreover, this superior arginine production within the body activates NO signaling, improving cardiovascular performance.

 

Citrulline Is More Effective at Decreasing Lactic Acid and Improving Exercise Performance

Exercise-induced muscle fatigue is due to many different factors, including the accumulation of certain metabolites within the muscle cell such as ammonia.7,8 During intense exercise, the conversion of adenosine triphosphate (ATP) into adenosine monophosphate (AMP) provides the necessary energy for muscular contraction while also increasing AMP levels. This greater amount of AMP due to muscular contraction results in higher ammonia levels because the body breaks down this additional AMP into ammonia, thus increasing ammonia levels. Subsequently, the accumulation of ammonia inhibits the metabolism of pyruvate in the muscle cell,9 reducing the production of energy while also increasing lactic acid production— which both have a negative influence on exercise performance.

Both citrulline and arginine play key roles in the biochemical pathway known as the urea cycle that reduces ammonia levels by converting ammonia into urea. Therefore, citrulline and arginine supplementation should reduce ammonia and lactic acid production in muscle tissue during exercise, facilitating exercise performance. However, a study by Sugino et al.10 showed even though arginine consumption does decrease ammonia, it does not improve exercise performance. Yet another investigation by Takeda et al.11 found that consuming citrulline reduced ammonia production during high-intensity exercise. More importantly, the researchers also found that citrulline decreased lactic acid production while significantly improving exercise performance in comparison to arginine. Taken together, these findings show that citrulline, and not arginine, improves performance during high-intensity exercise.

 

Citrulline Is More Anabolic

While much of the scientific literature shows that the amino acid leucine is one of the most prominent stimulators of the enzyme mTOR, which drives muscle protein synthesis and muscle growth, more recent studies show that arginine also has the ability to activate mTOR-driven protein synthesis in muscle.12 Because citrulline consumption more adeptly raises plasma arginine levels in comparison to arginine consumption4, citrulline should also trigger greater muscle protein synthesis than arginine.

In order to examine whether citrulline was more anabolic than arginine, several independent studies looked at the ability of citrulline to increase muscle growth and strength. In the first study, Osowska et al.13 showed that citrulline supplementation increased muscle protein synthesis. A second study by Le Plenier et al.14 confirmed that citrulline modulated protein synthesis through mTOR, because the effect was neutralized when the muscles supplied with citrulline were also incubated with the potent mTOR-inhibitor rapamycin. While these studies clearly show that citrulline enhances muscle growth, another study by Perez-Guisado et al.15 also demonstrated that citrulline consumption increased muscle strength. In this study, 41 men performed 8 sets of flat barbell bench presses at 80 percent of their 1-repetition maximum to failure, with half of the men given 8 grams of citrulline malate while the other half received a placebo. The group receiving citrulline malate was able to perform more repetitions for all 8 sets while also reporting much less muscle soreness. All in all, these studies clearly show that citrulline's ability to enhance muscle growth also improves strength in high-intensity weightlifting while also mitigating post-exercise muscle soreness. Based on the scientific research, 6-8 grams per dose of citrulline malate is most effective for increasing strength and muscle growth.

Although citrulline and arginine both stimulate NO production for greater muscular endurance while also stimulating mTOR-driven muscle growth, citrulline has clearly been shown to be a much more potent activator of both functions because of better bioavailability. Furthermore, citrulline’s greater activity produces the additional benefit of increased strength— making it an ideal choice for any bodybuilder or weightlifter wanting to build lean, ripped muscle.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

 

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