Nutrition Supplements

Citrulline vs. Arginine


Which amino acid provides the most powerful pump?

If you’ve read the labels of many preworkout products you may have noticed that fewer products are using arginine and more products are using citrulline. Some of you may be surprised by this since arginine is the amino acid that literally started the NO-booster supplement craze back in the late 90’s. Back then NO-boosters were simply arginine, mainly in the form of arginine alpha-ketoglutarate. That’s because in the body arginine is readily converted to nitric oxide (NO). Today we know a host of other ingredients that also help to increase NO production. But why is citrulline replacing arginine?

To answer that, I’ll have to get a bit deeper into the science behind citrulline.

You will notice two main forms of citrulline being used in products today – L-citrulline and citrulline malate. L-citrulline is the free form version of the amino acid citrulline. Citrulline malate is the amino acid citrulline attached to a molecule of malic acid (malate). Research confirms that both citrulline and citrulline malate provide significant increases in exercise performance… but only when enough of them are taken. In the gym, my other lab, I’ve found that when working with doses found in most supplements, anywhere from 1-3 grams, L-citrulline provides more of a potent pump than citrulline malate. Citrulline malate, on the other hand, provides more of a strength and endurance boost during workouts than L-citrulline does. However, if you increase the dose of citrulline malate (with a ctrulline malate product that delivers citrulline at a 2:1 ratio of malate) to about 6 grams or more, it delivers significant improvements in muscle strength and endurance while increasing the muscle pump like you wouldn’t believe. Let’s take a closer look at the research that further supports what I’ve seen in the gym.

Citrulline is an amino acid that is closely related to arginine.

Most of you should know the arginine-nitric oxide pathway, which is utilized by the body to convert arginine into nitric oxide (NO) with help from the enzyme nitric oxide synthase (NOS) to catalyze the reaction. Increasing NO levels in blood vessels relaxes the blood vessels, allowing them to widen or dilate. Dilated blood vessels deliver more blood flow to tissues like muscle fibers. The two main benefits of greater blood flow to muscle fibers is better exercise energy/endurance and bigger muscles pumps during workouts. The greater endurance and energy is due to the fact that pushing more blood to working muscles delivers them more oxygen and more nutrients. It enhances muscle pump during workouts due to the fact that the blood is more than 50% water. When you train, your muscle cells create waste products that pull water into them. With greater blood flowing to the muscles there is more water that the muscle cells can draw into them, resulting in a bigger muscle pump. While some experts feel that the muscle pump has no true physiological significance, the truth is that it can lead to long-term muscle growth. This is due to the fact that the bigger muscle pump places a bigger stretch on the membranes of the muscle cells. This stretch signals chemical reactions that instigate long-term muscle growth by increasing muscle protein synthesis. Some experts also argue that NO boosters offer no benefit to healthy individuals, especially during exercise. And it’s hard to argue with them if you look just at the research. Studies on NO-boosting ingredients, like arginine, show mixed results. However, in the gym with thousands of men and women, I have seen definite benefits that include greater strength and endurance, bigger muscle pumps and greater muscle growth. And one of the more recent studies on arginine reported that subjects consuming arginine 30 minutes before a biceps workout increased biceps blood volume during the workout by over 100%.

Citrulline appears to be an even better NO booster than arginine.

This has been shown in a couple of studies. The first one found that subjects taking equivalent doses of citrulline and arginine had higher arginine blood levels when they took citrulline versus when they took arginine.  A later study from German researchers reported that it took just half the amount of citrulline as arginine to raise arginine blood concentrations of arginine to an equivalent level. The German researchers also found that a 3 grams dose of citrulline produced the highest increase in arginine and NO levels. The greater effectiveness of citrulline versus arginine itself appears to be due to excessive breakdown of arginine in the body after it is consumed. This is due to the enzyme arginase that resides mainly in the intestines and liver. In fact, one study suggested that the amount of arginine consumed from oral supplements that was utilized in NO production was less than 1% of that consumed. Citrulline bypasses the liver, unlike arginine, and is not subject to breakdown by arginase. Therefore, using citrulline in place of arginine allows for higher arginine levels and higher NO production. One study found that over 80% of L-citrulline is converted to arginine in the blood vessels. And a study in professional cyclists showed that those supplementing with citrulline had a significant increase in NO production during exercise.

In addition to boosting NO levels, using citrulline to increase arginine levels in the body can also elevate growth hormone (GH) levels.

This works through arginine’s ability to inhibit the hormone growth hormone inhibiting hormone (GHIH) or somatostatin, which normally inhibits GH production. By inhibiting this hormone that inhibits GH, arginine increases the production and release of GH from the anterior pituitary gland, which leads to higher blood levels of GH. Spanish researchers reported higher GH levels in athletes during exercise when taking citrulline malate beforehand. Having higher GH levels during workouts may promote greater gains in muscle size and strength. It can also encourage greater fat burning during workouts. This is due to an increase in lipolysis, which means that GH encourages a greater release of fat from fat cells so that it can be burned away for fuel during the workout.

Citrulline also has the ability to promote exercise endurance and blunt fatigue through its ability to enhance the removal of ammonia and lactate from the blood.

This leads to a faster recovery between sets and can allow for greater muscle endurance. Taking citrulline in the form of L-citrulline malate also provides the additional benefit of malate, which is involved in the Krebs cycle to generate energy aerobically in the form of ATP (adenosine triphosphate). ATP is the energy currency of every cell. In muscle cells it is used to fuel muscle contractions, such as during exercise. Research in exercising humans shows that citrulline malate significantly improves the amount of ATP that the muscles are able to regenerate and enhances the rate that phosphocreatine (PCr) is regenerated. Phosphocreatine is what creatine is converted into inside the muscle cells through the addition of a high-energy phosphate group. Creatine donates this phosphate group during intense exercise, such as weight lifting, to produce ATP quickly to power muscle contractions that are required to lift the weight. This means that supplementing with citrulline malate can increase endurance to allow you to go longer, but also allow you to recover faster between sets, helping you to complete more reps per set later in your workouts. In fact, one study from Spain reports that subjects performing bench presses were able to complete more than 50% more reps from set 3 on for a total of 8 sets.

Jim’s take-home points:

Your best bet is to look for preworkout products that provide at least 6 grams of citrulline malate at a 2:1 ratio of citrulline to malate (provides 4 grams of citrulline) . That way you get enough citrulline for pumps and the citrulline malate combo for greater energy.


Author: Jim Stoppani



Haussinger, D. Control of protein turnover by the cellular hydratation state. Ital J Gastroenterol 25, 42–48, 1993.

Alvares, T. S., et al. Acute l-arginine supplementation increases muscle blood volume but not strength performance. Appl Physiol Nutr Metab. 2012 Feb;37(1):115-26.

Kuhn, K. P., et al. Oral citrulline effectively elevates plasma arginine levels for 24 hours in normal volunteers. Circulation 2002; 106: II1–766S.

Schwedhelm, E., et al. “Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism,” British Journal of Clinical Pharmacology, 65(1):51-9, 2008.

Morris, S. M., Jr. Enzymes of arginine metabolism. J Nutr 2004; 134: 2743S–7S.

Castillo, L., et al. Splanchnic metabolism of dietary arginine in relation to nitric oxide synthesis in normal adult man. Proc Natl Acad Sci USA 1993; 90: 193–7.

Böger, R. H., et al, Hypercholesterolemia impairs basal nitric oxide synthase turnover rate: a study investigating the conversion of L-[guanidino-15N2]-arginine to 15N-labeled nitrate by gas chromatography-mass spectrometry. Nitric Oxide 2004; 11: 1–8.

Solomonson, L. P., et al. The caveolar nitric oxide synthase/arginine regeneration system for NO production in endothelial cells. J Exp Biol 206:2083–2087, 2003.

Sureda, A., et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35.

Sureda, A., et al. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010 Sep;110(2):341-51.

Sanchez-Gonzalez MA., et al. The effects of short term L-citrulline supplementation on wave reflection responses to cold exposure with concurrent isometric exercise. Am J Hypertens. 2013 Apr;26(4):518-26.

El-Bassossy HM, Arginase inhibition alleviates hypertension in the metabolic syndrome. Br J Pharmacol, in press, 2013.

Takeda, K., et al. Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo). 2011;57(3):246-50.

Bendahan, D., et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002 Aug;36(4):282-9.

Giannesini, B., et al. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol. 2011 Sep 30;667(1-3):100-4.

Sureda, A., et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35.

Goubel, F., et al. Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins. Can J Physiol Pharmacol. 1997 Mar;75(3):205-7.

Callis, A., et al. Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung. 1991 Jun;41(6):660-3.

Pérez-Guisado, J. and Jakeman, P. M. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010 May;24(5):1215-22.