Verdict: Citrulline did not improve aerobic performance in a 2022 meta-analysis, so dietary nitrate is the better-supported nitric oxide option
Safety: Usually well tolerated, but arginine can upset the stomach and both can add to blood pressure medication
Key takeaways
Citrulline and arginine are amino acids that feed the body's own nitric oxide production, which is a different route from dietary nitrate
A 2022 meta-analysis of 10 trials found no clear benefit of citrulline for aerobic performance, oxygen uptake or perceived effort
Arginine trials suggest small blood pressure reductions, but anyone with high blood pressure should talk to a doctor rather than self-treat
"Nitric oxide booster" is one of the most common labels in the sports supplement aisle. Most of these products contain L-citrulline, L-arginine or both, sometimes with beetroot. The idea is simple: more nitric oxide, wider blood vessels, more oxygen to the muscles. The evidence is much less tidy.
What it is
Nitric oxide is a signalling molecule that relaxes blood vessels and influences how muscles use oxygen. The body makes it in two main ways. The first uses the amino acid arginine, via enzymes called nitric oxide synthases. Citrulline, found in watermelon, is converted into arginine in the kidneys, so it is an indirect arginine source. The second route uses dietary nitrate from beetroot and leafy greens, which mouth bacteria and the body convert to nitrite and then nitric oxide. These are different pathways, and they have very different evidence behind them.
Does it raise VO2max?
No study shows that citrulline or arginine raises VO2max in healthy people. VO2max is set mainly by how much blood your heart pumps and how much oxygen that blood carries (see what limits VO2max). A supplement that widens blood vessels a little does not change that ceiling. A 2022 meta-analysis on citrulline also found no effect on oxygen uptake kinetics.
Does it improve endurance performance?
Citrulline: Viribay and colleagues (Nutrients, 2022) pooled 10 placebo-controlled trials. They found no significant effect on aerobic performance (standardised mean difference 0.15, not significant), perceived effort, oxygen uptake kinetics or lactate. Their conclusion was that citrulline "did not prove to have any benefits" for aerobic exercise, with only a possible trend for longer protocols. A 2021 critical review of citrulline malate (Gough et al.) called the results for both resistance and high-intensity exercise "equivocal", partly because some products did not contain the citrulline-to-malate ratio stated on the label.
Arginine: an earlier meta-analysis by the same group (Viribay et al., 2020) reported improvements in aerobic and anaerobic tests, but the aerobic result was very heterogeneous, and a 2025 published comment criticised the analysis for errors that distort the pooled effects (Trexler, Nutrients 2025). Treat that headline number with caution.
Compared with beetroot: a meta-analysis of 80 studies (Senefeld et al., 2020) found a clear but small benefit of dietary nitrate in recreationally active young men, and no effect in well-trained endurance athletes. In a head-to-head trial, beetroot juice raised blood nitrate/nitrite levels far more than citrulline malate, although neither improved leg-extension performance (Trexler et al., 2019). If you want a nitric oxide product, the beetroot nitrate evidence is the stronger bet.
How it is used in studies
- Citrulline malate: a single 8 g dose about an hour before exercise is the most common protocol.
- Pure L-citrulline: in a one-week dosing study, up to 3 g twice a day raised blood arginine more effectively than the same amounts of arginine (Schwedhelm et al., 2008).
- Combinations: one trial gave 1.2 g citrulline plus 1.2 g arginine a day for a week and found slightly higher power in a 10-minute cycling test (Suzuki et al., 2019). It was a single small study.
- Arginine: doses vary widely. Much of an oral dose is broken down in the gut before it reaches the circulation, which is why citrulline is often preferred.
Blood pressure: meta-analyses of arginine (Dong et al., 2011; Shiraseb et al., 2022) report average reductions of roughly 5–6 mmHg systolic and about 2.6 mmHg diastolic. These are modest, the trials were mixed in quality, and they are not a substitute for treatment. Regular aerobic training also lowers blood pressure (see VO2max, heart disease and blood pressure).
Side effects, safety and anti-doping
Citrulline is usually well tolerated. Larger doses of arginine can cause bloating, nausea and diarrhoea. Because both can lower blood pressure, combining them with blood pressure drugs, nitrates for angina or erectile dysfunction medication may cause dizziness or low blood pressure. People with heart, kidney or liver conditions, and pregnant women, should talk to a doctor first. Neither is banned, but "pre-workout" blends are a known source of contamination, so athletes who compete should use third-party tested products. This page is not medical advice.
Who might benefit
Possibly no one, for endurance performance. Citrulline may be worth testing only if you enjoy experimenting and accept the evidence is weak, and it is cheap to stop if you notice nothing after a few weeks. For racing, caffeine and beetroot have far better support, and training still does the heavy lifting (see how to improve VO2max).
Bottom line
Citrulline and arginine are the main ingredients in "nitric oxide supplements", but meta-analyses show no reliable endurance benefit from citrulline and uncertain results for arginine. The small blood pressure effects of arginine are real but modest. Dietary nitrate is the nitric oxide supplement with the most evidence. Compare options on the supplements page.
Frequently asked questions
Do nitric oxide supplements work for endurance?
Evidence is weak for citrulline and inconsistent for arginine. Dietary nitrate from beetroot has much more support, with small benefits mainly in recreational athletes.
What are the benefits and side effects of nitric oxide supplements?
The proposed benefit is better blood flow, but performance gains are unproven for citrulline. Side effects are usually mild, such as stomach upset or diarrhoea with larger arginine doses.
Is a nitric oxide supplement good for blood pressure?
Meta-analyses of arginine report modest drops in blood pressure, but this is not a replacement for treatment. Talk to a doctor first, especially if you take blood pressure or erectile dysfunction medication.
L-citrulline or L-arginine, which is better?
Citrulline raises blood arginine more reliably than arginine itself, because much oral arginine is broken down in the gut. Neither has strong evidence for endurance performance.
Sources
- Viribay A, et al. Effects of citrulline supplementation on different aerobic exercise performance outcomes: a systematic review and meta-analysis. Nutrients. 2022;14(17):3479. doi:10.3390/nu14173479
- Viribay A, et al. Effects of arginine supplementation on athletic performance based on energy metabolism: a systematic review and meta-analysis. Nutrients. 2020;12(5):1300. doi:10.3390/nu12051300
- Trexler ET. Common errors in sports nutrition meta-analyses lead to distortion of pooled effect estimates. Comment on Viribay et al. Nutrients 2020, 12, 1300. Nutrients. 2025;17(14):2375.
- Gough LA, et al. A critical review of citrulline malate supplementation and exercise performance. Eur J Appl Physiol. 2021;121:3283–3295. doi:10.1007/s00421-021-04774-6
- Senefeld JW, et al. Ergogenic effect of nitrate supplementation: a systematic review and meta-analysis. Med Sci Sports Exerc. 2020;52(10):2250–2261. doi:10.1249/MSS.0000000000002363
- Trexler ET, et al. Effects of citrulline malate and beetroot juice supplementation on blood flow, energy metabolism, and performance during maximum effort leg extension exercise. J Strength Cond Res. 2019;33(9):2321–2329. doi:10.1519/JSC.0000000000003286
- Suzuki I, et al. A combination of oral L-citrulline and L-arginine improved 10-min full-power cycling test performance in male collegiate soccer players. Eur J Appl Physiol. 2019;119:1075–1084. doi:10.1007/s00421-019-04097-7
- Schwedhelm E, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51–59. doi:10.1111/j.1365-2125.2007.02990.x
- Dong JY, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959–965. doi:10.1016/j.ahj.2011.09.012
- Shiraseb F, et al. Effect of L-arginine supplementation on blood pressure in adults: a systematic review and dose-response meta-analysis. Adv Nutr. 2022;13(4):1226–1242. doi:10.1093/advances/nmab155