Citrulline (2-amino-5-(carbamoylamino) pentanoic acid) has found much favour with sports people (Sureda and Pons, 2012) in recent years. Here we discuss some of its health benefits especially in sports.

Synthesis And Metabolism Of Citrulline

It is an amino-acid type metabolite found in the urea cycle but is not a major component of proteins. It is synthesised in the intestine from ornithine and carbamoyl phosphate which is then turned to L-arginine and nitric oxide in the endothelial cells of the intestine. Another route of synthesis is from arginine via reactions catalysed by the enzyme nitric oxide synthase in what is known as the arginine-nitric oxide pathway. Citrulline is best regarded as a reservoir of arginine and is more effective at increasing plasma arginine levels than supplementing with arginine (Ochiai et al., 2012).

Running on treadmill in gym or fitness club - group of women and men exercising to gain more fitness
Hitting the treadmill. Copyright: kzenon / 123RF Stock Photo

It is claimed to optimise blood flow. Nitric oxide is heavily implicated in vasoprotection, improved blood flow, enhancing mental health and reducing physical tiredness. Citrulline is found to be better absorbed than arginine in nutrition.

Clinical Studies In Sports Health

One intriguing source of citrulline is watermelon juice and melons, which was shown in a study involving seven athletes, to reduce muscle soreness following intense exercise. Subjects were given natural watermelon juice and a juice enriched with L-citrulline or a placebo before the exercise (Tarazona-Diaz et al., 2013). The athletes drinking both types of juice had less muscle soreness than those taking the placebo. Citrulline had already been identified as a natural component of the juice back in 1930 (Mandel et al., 2005). Unpasteurised juice produced better results than the heat treated form which suggested other nutrients or citrulline in a more readily format might be the reason. The study has too few subject numbers to make the results statistically tight but more rigorously conducted studies with a larger number of subjects would be valuable.

Supplementation was also shown to decrease the time to exhaustion in a treadmill test (Hickner et al., 2006). The US Air Force also performed a randomised, double-blind cross over study feeding citrulline malate 6g/day. The study found there was no significant difference between the supplement and the placebo in any measure of respiration or time to exhaustion during incremental cycle ergometry.

Other Benefits

It has also been associated with a reduction in asthenia which is an abnormal lack of energy and feeling of lethargy, and for vasoprotection in sickle cell disease and atherosclerosis. The link has been made with reducing the impact of erectile dysfunction and diabetes.

There is also a certain amount of citrulline in the rinds of both melon and watermelon (Rimando and Perkins-Veazie, 2003).

Where Citrulline Does Not Have A Benefit

Citrulline supplementation does not have any significant impact or influence on blood glucose concentrations (Hickner et al., 2006; Sureda et al., 2010).

In summary, citrulline needs further research into its health benefits as the results are contentious.


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Sources of L-citrulline for use as a sports or health supplement. Most are offered as a salt with malate which helps with its solubility and may also contribute to metabolism.



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Hickner, R.C., Tanner, C.J., Evans, C.A., et al. (2006) L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med. Sci. Sports Exerc. 38 pp. 660-666. PMID: 16679980

Ochiai, M., Hayashi, T., Morita, M., Ina, K., Maeda, M., Watanabe, F., & Morishita, K. (2012). Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. International Journal of Cardiology155(2), pp. 257-261. PMID: 21067832

Mandel, H., Levy, N., Izkovitch, S., Korman, S.H. (2005) Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon). J. Inherit Metab Dis. 28 pp. 467-472.

Rimando, A.M., Perkins-Veazie, P. (2003) 19-3 Citruline found in watermelon rind. Technical Abstract 19-3 IFT Annual Mtg., July 12-16. Chicago, IL. USA.

Sureda, A., Córdova, A., Ferrer, M. D., Pérez, G., Tur, J. A., & Pons, A. (2010). L-citrulline-malate influence over branched chain amino acid utilization during exercise. European Journal of Applied Physiology, 110(2), pp. 341-351. PMID: 20499249

Sureda, A., Pons, A. (2012) Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients? Med Sport Sci. 59 pp. 18-28.

Tarazona-Díaz, M.P., Alacid, F., Carrasco, M., Martinez, I., Aguayo, E. (2013) Watermelon juice: potential functional drink for sore muscle relief in athletes. J. Agric Food Chem. 2013 Jul 29.

Walker TB, Zupan MF, Rutter MJ, Vojta CN. AFRL-RH-BR-TR-2010-0068. Does citrulline malate enhance physical performance? Air Force Research Laboratory, Human Effectiveness Directorate. October 2010. Accessed May 10th 2014

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