Citrulline malate is a dietary supplement that combines L-citrulline, a non-essential amino acid, with malate (malic acid), an intermediate of the cell’s energy-producing citric acid cycle. It is sold mainly as a pre-workout ingredient, with claims that it raises nitric oxide, delays fatigue and reduces muscle soreness.
The most important fact is that the effect is small and inconsistent. The largest meta-analysis to date, 30 randomized trials with 644 participants, found a small overall benefit (Hedges’ g = 0.16) rated low to very low certainty (Wang et al., Nutrients 2026). The European Food Safety Authority (EFSA) rejected a recovery claim for citrulline malate in 2012 (EFSA NDA Panel 2012).
This page summarizes what the clinical trials, meta-analyses and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Amino acid supplement (L-citrulline bound to malic acid) |
| Usual stated ratio | 2:1 citrulline to malate by weight |
| Route | Oral powder or capsules |
| Most studied dose | 8 g of citrulline malate, taken 40–60 minutes before exercise |
| Half-life | No formal elimination half-life published; plasma citrulline peaks in ≈0.5–1 h and amino acid levels return to baseline within 5–8 h |
| Key mechanism | Converted to arginine, the substrate for nitric oxide production |
| Medicinal use | Marketed as Stimol (Biocodex, France) for asthenia (fatigue states) |
| US status | Dietary supplement, not an approved drug |
| WADA status | Not named on the 2026 Prohibited List |
What it is
L-citrulline is an amino acid the body makes itself. Glutamine is its main precursor (Rougé et al., AJP-GI 2007). The kidneys then convert citrulline into arginine (Moinard et al., Br J Nutr 2008). Arginine is the raw material that nitric oxide synthase uses to make nitric oxide, a signal that relaxes blood vessels.
Malate is added for two reasons. It forms a stable salt with citrulline and neutralizes citrulline’s alkalinity, which helps storage and palatability (Chappell et al., JISSN 2018; Wang et al. 2026). It is also a citric acid cycle intermediate, and early researchers proposed that extra malate could boost aerobic energy production in muscle (Bendahan et al., Br J Sports Med 2002).
Citrulline malate has also been marketed as a medicine for asthenia (persistent fatigue). Russian clinical reports describe Stimol, a citrulline malate product from the French company Biocodex, given for fatigue syndromes (Fedorova, Zh Nevrol Psikhiatr 2000). These were small, uncontrolled studies.
The proposed ways it might help exercise are (Harnden et al., JISSN 2023; Bendahan et al. 2002):
- more arginine, and therefore more nitric oxide and blood flow to working muscle;
- buffering of ammonia, a by-product of hard exercise;
- more aerobic energy production from the malate part.
None of these has been shown to translate reliably into better performance, as the sections below explain.
Citrulline malate vs plain L-citrulline
| Form | Citrulline per 8 g serving | Notes |
|---|---|---|
| Citrulline malate, true 2:1 ratio | ≈5.3 g | The ratio used in most trials |
| Citrulline malate, 1.11:1 (measured in one product) | ≈4.2 g | See “Quality and labeling” below |
| L-citrulline | 8 g | No malate |
The per-serving figures come from the nuclear magnetic resonance (NMR) analysis in Chappell et al., JISSN 2018. A 2025 crossover trial directly compared the two forms at the same citrulline dose and found no benefit from either one (see below).
How it works in the body
Oral citrulline is well absorbed. Unlike oral arginine, it largely escapes breakdown by arginase enzymes in the gut and liver. In a randomized, double-blind crossover study in 20 healthy volunteers, one week of oral L-citrulline raised plasma arginine more effectively than oral arginine itself (Schwedhelm et al., Br J Clin Pharmacol 2008).
| Study | Dose | Key kinetic findings |
|---|---|---|
| Moinard et al. 2008, 8 healthy men | Single doses of 2, 5, 10 and 15 g L-citrulline | Peak arginine 146–303 μmol/L at 1.2–2.3 h; under 5% of citrulline lost in urine; at the highest doses arginine rose less than expected, suggesting the kidney’s conversion saturates |
| Schwedhelm et al. 2008, 20 healthy adults | 0.75–3 g L-citrulline twice daily for 1 week | Dose-dependent rise in plasma arginine; 3 g twice daily raised the arginine/ADMA ratio from 186 to 278; a half-life could not be calculated |
| Grannes et al. 2026, 6 healthy men (blood subgroup) | 6 g or 12 g citrulline malate | Peak serum citrulline 505 μM (6 g, at 30 min) and 882 μM (12 g, at 60 min); arginine peaked at 60 min |
ADMA (asymmetric dimethylarginine) is the body’s own inhibitor of nitric oxide synthase, so a higher arginine/ADMA ratio favors nitric oxide production. A review of amino acid kinetics reported that blood levels of citrulline and related amino acids generally return to baseline within 5–8 h, and that a meal delays the peak by 15–30 minutes (Cynober, J Nutr 2007).
Single doses of 2–15 g of L-citrulline did not change insulin or growth hormone levels (Moinard et al. 2008). There is no evidence that it has hormonal or anabolic effects.
Blood flow
Raising arginine does not reliably widen blood vessels. In the Schwedhelm study, no dose improved flow-mediated dilation (FMD, an ultrasound test of how well an artery widens) over baseline. In a 2026 crossover trial in 12 healthy young men, neither 6 g nor 12 g of citrulline malate changed FMD at 60 or 120 minutes, despite large rises in blood citrulline and arginine (Grannes et al., Front Physiol 2026).
Regulatory status
- United States: sold as a dietary supplement rather than as an approved drug (Vårvik et al., IJSNEM 2021).
- European Union: in 2012 EFSA reviewed a health claim submitted by Biocodex that citrulline malate speeds recovery from muscle fatigue after exercise. The panel concluded that a cause-and-effect relationship had not been established. Studies in patients with asthenia could not support the claim, and the one study in athletes had methodological limitations (EFSA NDA Panel 2012).
- Sport: citrulline and citrulline malate are not named on the WADA 2026 Prohibited List.
What the research shows
Most trials are small and short, and most use a crossover design. The most common protocol is a single 8 g dose taken 40–120 minutes before exercise (Wang et al. 2026). Results vary widely between studies, so the meta-analyses below are a better guide than any single trial.
Overall exercise performance
| Meta-analysis | Studies (n) | Outcome | Pooled effect |
|---|---|---|---|
| Wang et al. 2026 | 30 RCTs (644) | All performance outcomes, citrulline malate only | g = 0.16 (95% CI 0.05–0.27); low certainty |
| Same, acute single dose | 114 effect sizes | Performance | g = 0.16 (95% CI 0.02–0.30) |
| Same, repeated dosing (3–56 days) | 24 effect sizes | Performance | g = 0.13 (95% CI −0.01 to 0.28); not significant |
| Same | 19 effect sizes | Perceived exertion | g = −0.25 (95% CI −0.80 to 0.29); not significant |
| Trexler et al. 2019 | 12 studies (198) | High-intensity strength and power, any citrulline form | SMD 0.20 (95% CI 0.01–0.39) |
A standardized effect of 0.2 is conventionally considered small. In the 2026 analysis, the prediction interval ran from −0.37 to 0.69, meaning a future trial could plausibly find no effect or a negative one. Its authors concluded that reliable dosing, timing and target populations have not been established.
Repetitions to failure in strength training
This is the outcome with the most consistent signal. A meta-analysis of 8 double-blind trials (137 participants) found that 6–8 g of citrulline malate taken 40–60 minutes before training increased total repetitions by 3 ± 5, or 6.4% (Vårvik et al., IJSNEM 2021). The pooled effect was small (SMD 0.196). The lower-body subanalysis only tended toward significance (p = 0.051), and the upper-body effect was not significant.
Individual trials show how inconsistent the results are:
| Trial | Participants | Dose | Result |
|---|---|---|---|
| Pérez-Guisado & Jakeman 2010 | 41 men, crossover | 8 g CM | More bench press repetitions from the third set on, up to 52.9% more in the last set |
| Glenn et al. 2017 | 15 trained women, crossover | 8 g CM | Bench press 34.1 vs 32.9 reps; leg press 66.7 vs 55.1 reps |
| Chappell et al. 2018 | Recreationally active men and women, crossover | 8 g CM (measured ratio 1.11:1) | 90.9 reps on CM vs 94.0 on placebo; no difference |
| Martín-Olmedo et al. 2025 | 43 trained adults (21 women), crossover | 5.3 g L-citrulline, or 5.3 g citrulline + 2.7 g malate | Neither form improved strength, power or repetitions |
The 2025 trial is notable because it isolated the effect of malate. Adding malate to the same citrulline dose made no difference, and neither supplement beat placebo.
Maximal strength
A meta-analysis of 4 trials in resistance-trained adults found no overall effect of citrulline malate on maximal muscle strength (SMD 0.13, 95% CI −0.21 to 0.46), for either upper or lower limbs (Aguiar & Casonatto, J Diet Suppl 2022).
Endurance exercise
A meta-analysis of 9 trials (158 participants) found no effect of acute citrulline on time to exhaustion (SMD 0.03, 95% CI −0.27 to 0.33) or time to complete a set distance in young healthy adults (Harnden et al., JISSN 2023). In 10 well-trained men, 12 g of citrulline malate before repeated cycle sprints did not change sprint power or time to exhaustion (Cunniffe et al., JSCR 2016).
Muscle soreness and perceived effort
A meta-analysis of 13 trials (206 participants), most using 8 g of citrulline malate, found that citrulline reduced perceived exertion and muscle soreness at 24 h after exercise. It did not reduce soreness at 72 h or lower blood lactate (Rhim et al., J Sport Health Sci 2020). The Pérez-Guisado trial reported 40% less soreness at 24 and 48 h. However, in the Chappell trial soreness over 72 h was significantly higher on citrulline malate than on placebo.
Muscle energy metabolism
The malate rationale rests largely on one study. In 18 men who complained of fatigue, 6 g/day of citrulline malate for 15 days was followed by a 34% rise in the rate of oxidative ATP production during finger-flexion exercise and a 20% faster phosphocreatine recovery, measured by phosphorus magnetic resonance spectroscopy (Bendahan et al. 2002). Each man was compared with his own pre-supplement measurements; no placebo group is described.
Side effects and risks
Tolerability
Short-term use appears well tolerated in healthy adults:
- In the Moinard dose-ranging study, none of the 8 men had side effects after single doses of up to 15 g of L-citrulline.
- In 10 trained men given 12 g of citrulline malate, none reported gastrointestinal side effects (Cunniffe et al. 2016).
- In the 41-man Pérez-Guisado trial, 14.6% reported stomach discomfort after 8 g, the only side effect recorded.
Long-term safety data are lacking. A 2007 review noted that there had been no pharmacokinetic studies of long-term use in healthy people, and that a safe upper limit of daily intake had not been determined (Cynober 2007). The 2026 meta-analysis called for standardized adverse-event reporting in future trials.
Blood pressure
Because citrulline feeds nitric oxide production, it is often assumed to lower blood pressure. A meta-analysis of 5 interventions found no significant change in brachial systolic or diastolic blood pressure with L-citrulline (diastolic change −1.56 mmHg, 95% CI −4.32 to 1.20) (Mirenayat et al., Curr Hypertens Rep 2018). The trials cited on this page enrolled healthy volunteers; no formal drug-interaction studies were found, so effects in people taking blood pressure or erectile dysfunction medicines have not been characterized.
Quality and labeling
What is on the label may not be what is in the tub. Researchers used NMR spectroscopy to measure the citrulline-to-malate ratio in five UK products all labeled as 2:1 (Chappell et al., JISSN 2018):
| Product | Measured ratio | Citrulline per 8 g dose |
|---|---|---|
| A | 1.92:1 | 5.26 g |
| B | 1.62:1 | 4.95 g |
| C | 1.57:1 | 4.88 g |
| D | 1.51:1 | 4.81 g |
| E (used in the trial) | 1.11:1 | 4.21 g |
Only one product was close to its labeled ratio. The authors noted that underdosing could explain some negative trial results, and later reviews called for trials that verify supplement composition (Wang et al. 2026).
Key takeaways
- A precursor, not a hormone. Citrulline raises blood arginine more effectively than oral arginine does, but it does not change insulin or growth hormone and has no anabolic effect.
- Small, inconsistent performance effect. Pooled data show at most a small benefit (g ≈ 0.16–0.20), with low to very low certainty and wide variation between trials.
- Repetitions, not strength. The clearest signal is a few extra repetitions to failure (≈6%); maximal strength and endurance show no reliable benefit.
- Malate’s role is unproven. Adding malate to the same citrulline dose made no difference in a 2025 head-to-head trial, and EFSA rejected a recovery claim in 2012.
- Well tolerated short term. Single doses up to 15 g of citrulline caused no side effects in a small study; stomach discomfort is the main reported complaint.
- Labels can be inaccurate. In one analysis, only one of five products labeled 2:1 came close to that ratio; the worst held about 4.2 g instead of 5.3 g of citrulline per 8 g.
Sources
- Wang X, Fan X, Chang J, et al. Effects of citrulline malate supplementation on exercise performance: a systematic review and three-level meta-analysis. Nutrients. 2026;18(12):1881. PubMed.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on the substantiation of a health claim related to citrulline malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J. 2012;10(5):2699. PubMed.
- Rougé C, Des Robert C, Robins A, et al. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. 2007;293(5):G1061–G1067. PubMed.
- Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008;99(4):855–862. PubMed.
- Chappell AJ, Allwood DM, Johns R, et al. Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. J Int Soc Sports Nutr. 2018;15(1):42. PubMed.
- Bendahan D, Mattei JP, Ghattas B, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002;36(4):282–289. PubMed.
- Fedorova VI. Autonomic disorders in persons with asthenic syndrome and their correction with citrulline malate [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2000;100(4):32–36. PubMed.
- Schwedhelm E, Maas R, Freese R, 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. PubMed.
- Grannes J, Callender NA, Gonzalez AM, et al. Acute effect of citrulline malate on flow-mediated dilation and serum pharmacodynamics in healthy young males. Front Physiol. 2026;17:1773582. PubMed.
- Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr. 2007;137(6 Suppl 2):1646S–1649S. PubMed.
- Vårvik FT, Bjørnsen T, Gonzalez AM. Acute effect of citrulline malate on repetition performance during strength training: a systematic review and meta-analysis. Int J Sport Nutr Exerc Metab. 2021;31(4):350–358. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. In effect from January 1, 2026. WADA.
- Trexler ET, Persky AM, Ryan ED, et al. Acute effects of citrulline supplementation on high-intensity strength and power performance: a systematic review and meta-analysis. Sports Med. 2019;49(5):707–718. PubMed.
- Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215–1222. PubMed.
- Glenn JM, Gray M, Wethington LN, et al. Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. Eur J Nutr. 2017;56(2):775–784. PubMed.
- Martín-Olmedo JJ, Miras-Moreno S, Cuadra-Montes K, et al. Malate or not? Acute effects of L-citrulline versus citrulline malate on neuromuscular performance in young, trained adults: a randomized, double-blind, placebo-controlled crossover trial. Int J Sport Nutr Exerc Metab. 2025;35(2):89–98. PubMed.
- Aguiar AF, Casonatto J. Effects of citrulline malate supplementation on muscle strength in resistance-trained adults: a systematic review and meta-analysis of randomized controlled trials. J Diet Suppl. 2022;19(6):772–790. PubMed.
- Harnden CS, Agu J, Gascoyne T. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. J Int Soc Sports Nutr. 2023;20(1):2209056. PubMed.
- Cunniffe B, Papageorgiou M, O’Brien B, et al. Acute citrulline-malate supplementation and high-intensity cycling performance. J Strength Cond Res. 2016;30(9):2638–2647. PubMed.
- Rhim HC, Kim SJ, Park J, et al. Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: a systematic review and meta-analysis. J Sport Health Sci. 2020;9(6):553–561. PubMed.
- Mirenayat MS, Moradi S, Mohammadi H, et al. Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of clinical trials. Curr Hypertens Rep. 2018;20(11):98. PubMed.