L-citrulline is a non-essential (not necessary in diet) non-proteinogenic (not a building block for muscles) amino acid, which occurs in human diet only in small quantities. Its main natural source is watermelon, but the body can also synthesize it itself. In the field of sports nutrition, L-citrulline has gained great popularity due to its ability to increase arginine levels in the body and support nitric oxide (NO) production.
Mechanism of action: Arginine cycle
The main significance of citrulline lies in its role in amino acid metabolism:
- Arginine synthesis: Citrulline is used in the body for arginine synthesis and accounts for up to 60% of de novo arginine synthesis in the organism.
- Nitric oxide (NO) production: Arginine is then converted into nitric oxide and citrulline by the enzyme nitric oxide synthase (NOS), and this is where the benefits for athletes begin.
- Nitric oxide (NO): acts as a powerful vasodilator, which widens blood vessels, thereby improving blood flow, oxygen supply, and nutrients to working muscles. It also reduces the amount of ATP needed to develop muscle strength, which the athlete will feel in terms of better endurance and regeneration. (Bescós et al. 2012).
Why choose L-citrulline instead of L-arginine?
L-citrulline is a much more effective provider of nitric oxide than L-arginine alone. There are two reasons for this. The first reason is that, unlike arginine, L-citrulline does not cause gastrointestinal problems (nausea, cramps) even at higher doses (6 g). The second reason is the fact that a large part of orally administered L-arginine is broken down already in the digestive tract and liver, where the enzyme arginase converts arginine to ornithine and urea. Citrulline can prevent this breakdown by blocking the enzymatic activity of arginase. It is scientifically proven that oral intake of L-citrulline for 7 days increases plasma arginine concentration and NO production, which then has the above-mentioned benefits for sports performance (Schwedhelm et al., 2008).
Effect on athletic performance and regeneration
Research on citrulline supplementation suggests several key benefits:
- Reduction of ammonia levels: A study by Aguayo et al. 2021, showed that citrulline intake increases plasma urea concentration and simultaneously suppresses hyperammonemia (increased ammonia levels) induced by exercise. Ammonia is associated with the onset of muscle fatigue, so its more efficient removal prolongs physical performance.
- Improved endurance: Seven days of supplementation with 6 g of L-citrulline daily led to a slight improvement in time trial performance and a reduction in perceived effort in trained cyclists (Stanelle, McLaughlin and Crouse 2020)
- High-intensity performance: Other studies, e.g., by Bailey et al. 2015, report improved performance during high-intensity exercise after seven days of consuming 6 g of citrulline daily, with the last dose 1-2 hours before exercise.
Dosage and timing
The difference between acute and chronic use is crucial (Viribay et al. 2022):
- Chronic use (with effect): Most studies that demonstrated a positive effect on performance (e.g., in cycling or running) used a dosage of 3.4 to 6.0 g of citrulline daily for 6 to 16 days
- Acute use: Conversely, a single dose administered 1–3 hours before exercise (ranging from 1 to 12 g of citrulline) typically did not lead to an immediate improvement in aerobic performance.
- Recommendation for athletes: Based on available data, the most optimal supplementation protocol appears to be a loading phase of 6 g of citrulline daily for at least 6 days, with the last dose taken approximately 1–2 hours before physical activity. A suitable product for the last dose could also be, for example, a pre-workout that combines caffeine and L-citrulline.
Conclusion for athletes
L-Citrulline is currently considered one of the few supplements with scientifically proven ergogenic (having an effect on physical performance) potential in terms of increasing arginine levels and NO production without digestive side effects. Therefore, we definitely recommend including it in your dietary supplement routine for improving physical performance.
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Sources of information
- Bescós, R., A. Sureda, J.A. Tur, and A. Pons. 2012. The effect of nitric-oxide-related supplements on human performance. Sports Med 42: 99-117.
- Schwedhelm, E., R. Maas, R. Freese, D. Jung, Z. Lukacs, A. Jambrecina, W. Spickler, F. Schulze, and R.H. Böger. 2008. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: Impact on nitric oxide metabolism. Br J Clin Pharmacol 65: 51-59.
- Aguayo, E. A. Martínez-Sánchez, B. Fernández- Lobato, and F. Alacid. 2021. L-citrulline: A non-essential amino acid with important roles in human health. Appl Sci 11:3293.
- Stanelle, S.T., K.L. McLaughlin, and S.F. Crouse. 2020. One week of L-citrulline supplementation improves performance in trained cyclists. J Strength Cond Res 34(3):647-652.
- Bailey, S.J., J.R. Blackwell, T. Lord, A. Vanhatalo, P.G. Winyard, and A.M. Jones. 2015. L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol 119(4):385-395.
- Jeukendrup, A., & Gleeson, M. (2025). Sport nutrition (4th ed.). Human Kinetics.
- Viribay, A., J. Fernández-Landa, A. Castañeda-Babarro, P.S. Collado, D. Fernández-Lázaro, and J. Mielgo-Ayuso. 2022. Effects of citrulline supplementation on different aerobic exercise performance outcomes: A systematic review and meta-analysis. Nutrients 14(17):3479.
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