Citrulline is a non-essential amino acid, meaning that the body can manufacture it from other nutrients. Within the body, citrulline is converted to the amino acid L-arginine. Arginine creates nitric oxide (NO), a chemical that dilates blood vessels. Some of the proposed uses of citrulline supplements are based on raising levels of arginine. Citrulline also plays a role in a physiological process called “the urea cycle,” in which toxic ammonia is converted to urea.
The body manufactures citrulline from the essential amino acid glutamine. Deficiency of citrulline is unlikely to occur.
A typical dose of citrulline is 6–18 grams daily. It is commonly sold in the form of citrulline malate.
Dilated blood vessels improve blood flow, blood pressure, and oxygen delivery to muscles. This is the basis of using it to enhance sports performance. Much of the science to support citrulline supplements for this purpose is promising, but the trials were small (less than 25 people), which makes it harder to determine if the results are conclusive or just random chance. In addition, the participants were active on a regular basis or trained athletes so it is not clear if these benefits would extend to people with all levels of fitness.
A handful of randomized trials found that citrulline supplements did reduce muscle fatigue while improving endurance, overall performance, and time to recovery when compared to placebo1-5,7,9 . One randomized trial found similar results using watermelon juice enriched with citrulline.8 However, one trial found no benefit with consuming watermelon juice concentrate alone.6
Nitric oxide (NO) sensitivity plays a part in the ability to achieve and maintain an erection. This could lead one to believe that citrulline supplements may be helpful for men with impotence. One randomized trial found this to be the case when compared to placebo. Again, the trial had less than 25 participants with mild impotence, which makes it less reliable. In addition, placebos alone can be effective for some men. It was not indicated if impotence related to physical or psychological factors.10
As a naturally occurring amino acid, citrulline is believed to be safe. However, maximum safe doses in young children, pregnant or nursing women, or people with severe liver or kidney disease have not been established.
1. Bendahan D, Mattei JP, Ghattas B, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002;36:282–9.
2. Callis A, Magnan de Bornier B, Serrano JJ, 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;41:660–3.
3. Hickner RC, Tanner CJ, Evans CA et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006;38:660-6.
4. Suzuki T, Morita M, Kobayashi Y, Kamimura A. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. J Int Soc Sports Nutr. 2016;13:6.
5. Chen IF, Wu HJ, Chen CY, Chou KM, Chang CK. Branched-chain amino acids, arginine, citrulline alleviate central fatigue after 3 simulated matches in taekwondo athletes: a randomized controlled trial. J Int Soc Sports Nutr. 2016;13:28.
6. Bailey SJ, Blackwell JR, Williams E, et al. Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans. Nitric Oxide. 2016;59:10-20.
7. Figueroa A, Wong A, Jaime SJ, Gonzales JU. Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance. Curr Opin Clin Nutr Metab Care. 2017;20(1):92-98.
8. Martínez-Sánchez A, Ramos-Campo DJ, Fernández-Lobato B, Rubio-Arias JA, Alacid F2, Aguayo E. Biochemical, physiological, and performance response of a functional watermelon juice enriched in L-citrulline during a half-marathon race. Food Nutr Res. 2017;61(1):1330098.
9. Kiyici F, Eroğlu H, Kishali NF, Burmaoglu G. The effect of citrulline/malate on blood lactate levels in intensive exercise. Biochem Genet. 2017 Jun 29 [epub ahead of print].
10. Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011;77(1):119-122.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 8/11/2017
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