A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • More pump and blood flow during training

    No benefit

    Muscle & performance · healthy · Human, randomised

    No greater muscle swelling after bench press in a placebo-controlled study [7]; evidence for acute vasodilation and muscle blood flow sparse and contradictory [5]; FMD unchanged in young healthy people [3]. The data basis on the pump itself is small.

  • Better vascular function

    Small benefit

    Heart & blood vessels · healthy (middle-aged and older) · Human, randomised

    Meta-analysis of 8 RCTs: better FMD, arterial stiffness overall not significantly changed [6]; no FMD improvement in young healthy people [3].

  • More strength and performance in intense efforts

    Small benefit

    Muscle & performance · healthy · Human, randomised

    Meta-analyses: SMD 0.20 for strength and power [8], g 0.16 for citrulline malate with low to very low certainty [10]; one repetition study found no effect [7].

  • More endurance

    No benefit

    Muscle & performance · healthy · Human, randomised

    Two meta-analyses found no significant effect on aerobic performance, time to exhaustion or time trials [11][12].[11][12]

Mechanism of action

Evidence map: L-Citrulline

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Citrulline is formed in the gut from glutamine, enters the blood and is converted back to arginine in the kidney via argininosuccinate synthetase; circulating citrulline is thus a masked form of arginine that escapes uptake by the liver [1]. Swallowed arginine, by contrast, reaches the circulation only to about 20%, as a study with oral and intravenous administration in 10 healthy people showed [2]. In a double-blind, placebo-controlled crossover study with 20 healthy people, oral citrulline raised the area under the curve and peak value of plasma arginine in a dose-dependent manner more than arginine did; the authors attribute this to the breakdown of arginine by arginase in the intestinal wall [3]. At the same time, the ratio of arginine to the endogenous NO synthase inhibitor ADMA rose, as did urinary nitrate and cGMP as markers of nitric oxide production; however, no treatment improved flow-mediated dilation (FMD) compared with baseline [3]. In a pharmacokinetic study with 8 men, no side effects occurred; at the highest doses, arginine rose less than expected, presumably because the conversion in the kidney is saturable [4].

Whether more arginine also means more blood flow in muscle is open. A review found only sparse and contradictory evidence for acute improvements in vasodilation and muscle blood flow after citrulline [5]. A meta-analysis of 8 RCTs with 176 middle-aged and older people, by contrast, found better FMD but no significant effect on arterial stiffness [6]. In trained young men, citrulline malate changed neither the number of repetitions in the bench press nor the muscle swelling after training, i.e., the “pump” [7].

For strength and power, a meta-analysis of 12 studies with 198 participants showed a small benefit (SMD 0.20), with the confidence interval of every single study including zero [8]. The widely cited study with 41 men, in which citrulline malate increased repetitions in the last set by 52.9% and reduced muscle soreness by 40% [9], was not confirmed at this magnitude. A meta-analysis of 30 RCTs on citrulline malate found a small overall improvement (g 0.16) with wide prediction intervals and low to very low certainty of evidence according to GRADE and calls for studies with verified composition of the preparations [10]. For endurance, two meta-analyses showed no benefit: neither for aerobic performance measures, oxygen uptake and perceived exertion [11] nor for time to exhaustion or time trials in young healthy people [12].

Targets

TargetTypeActionKey dataEvidence
Argininosuccinate synthetase (mainly kidney)EnzymeBindingSubstrate; conversion to arginine, saturable at high doses Human, non-randomised[1][4]
NO synthase (indirectly via more arginine)EnzymeActivatorArginine/ADMA 186 → 278; urinary nitrate 92 → 125 µmol/mmol creatinine (RCT, highest dose level) Human, randomised[3]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowunclear · FMD unchanged in young healthy people, improved in middle-aged and older people; acute muscle blood flow and pump not documented[3][5][6][7]
  • Nitric oxide↑ · Plasma arginine, arginine/ADMA ratio and urinary nitrate and cGMP rise (placebo-controlled crossover study)[3]
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeno data
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · L-citrulline

    Escapes breakdown by arginase in the intestinal wall and uptake by the liver and is converted to arginine in the kidney [1][3]; raises plasma arginine more than oral arginine [3], whose bioavailability is only about 20% [2]. Less than 5% is excreted in urine; at high doses, the conversion is saturable [4].[1]

    Human, randomised

  • Oral (swallowed) · Citrulline malate

    Used in most performance studies; one meta-analysis calls for studies with verified composition of the preparations [10]. Direct comparisons of the pharmacokinetics with pure citrulline were not found.

    Human, randomised

Human studies

  • Citrulline vs. arginine, pharmacokinetics and NO

    RCT, double-blind, placebo-controlled, crossover · healthy · n = 20 · 1 week each

    Measured: Plasma arginine, arginine/ADMA, urinary nitrate, cGMP, FMD

    Result: Citrulline raised arginine more than arginine did (p < 0.01); arginine/ADMA, nitrate and cGMP rose; FMD not improved by any treatment.[3]

    Human, randomised

  • Meta-analysis strength and power

    systematic review and meta-analysis of placebo-controlled studies · healthy · n = 198 · acute dose

    Measured: Strength and sprint performance

    Result: SMD 0.20 (95% CI 0.01–0.39), low heterogeneity; all individual studies with zero in the confidence interval.[8]

    Human, randomised

  • Meta-analysis citrulline malate

    systematic review and three-level meta-analysis of 30 RCTs · healthy · n = 644 · acute and chronic

    Measured: Performance, perceived exertion

    Result: g 0.16 (p = 0.01), wide prediction intervals; perceived exertion unchanged; GRADE low to very low.[10]

    Human, randomised

  • Meta-analysis endurance in young healthy people

    systematic review and meta-analysis of RCTs · healthy · n = 158 · acute dose

    Measured: Time to exhaustion, time trials

    Result: SMD 0.03 and −0.07, respectively, no significant effect.[12]

    Human, randomised

  • Citrulline malate and bench press (repetition)

    RCT, double-blind, placebo-controlled, crossover · healthy (strength training, men) · n = 12 · single dose

    Measured: Repetitions, performance, muscle thickness, subjective energy

    Result: No increase in performance, no greater muscle swelling.[7]

    Human, randomised

  • Citrulline malate and bench press (original study)

    RCT, double-blind, crossover · healthy (men) · n = 41 · single dose

    Measured: Repetitions to exhaustion, muscle soreness

    Result: 52.9% more repetitions in the last set, 40% less muscle soreness; stomach complaints in 14.6%.[9]

    Human, randomised

Risks and warnings

  • Gastrointestinal complaints

    In one performance study, 14.6% of participants reported stomach complaints after citrulline malate [9]; in a pharmacokinetic study with 8 men, no side effects occurred [4].

    Human, randomised

  • Uncertain product composition and study quality

    The meta-analysis on citrulline malate rates the certainty of evidence as low to very low and calls for studies with verified composition of the preparations [10].

    Human, randomised

Fact check: common claims

  • supported

    “Citrulline raises blood arginine more than arginine itself”

    Placebo-controlled crossover study with direct comparison [3]; explainable by the breakdown of arginine before it reaches the circulation [2][3] and the conversion of citrulline in the kidney [1].

  • not supported

    “Citrulline provides a stronger pump”

    No greater muscle swelling in a placebo-controlled study [7]; evidence for acutely better muscle blood flow sparse and contradictory [5].

  • not supported

    “Citrulline malate increases the number of repetitions by over 50%”

    Single finding [9]; a similar study found no effect [7], meta-analyses show only small effects with low certainty [8][10].

  • not supported

    “Citrulline improves endurance performance”

    Two meta-analyses without a significant effect [11][12].

  • supported

    “Citrulline increases nitric oxide production”

    Urinary nitrate and cGMP as well as the arginine/ADMA ratio rose compared with baseline in a randomized study [3]; whether this improves performance is open [5].

Pharmacokinetics

Absorption
Well absorbed orally; bypasses gut arginase and liver [1][3]. Peak arginine values after about 1.2 to 2.3 hours depending on the dose [4].
Half-life
Not verified.
Metabolism
Conversion to arginine via argininosuccinate synthetase, mainly in the kidney; saturable at high doses, after which citrulline accumulates in plasma; ornithine rises as well [1][4].
Entry into the brain
Not verified.

Legal status

Germany
Not verified.
EU
Not verified.
USA
Not verified.
Other countries
Has long been used in inherited urea cycle disorders [1]; legal status as a dietary supplement not checked.

Open questions

  • Why do more arginine and nitric oxide not lead to measurably better vascular function or performance in young healthy people?
  • Do commercially available citrulline malate preparations contain the stated ratio of citrulline and malate?
  • Is the small effect on strength and power reproducible in large, preregistered studies?

References

  1. Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, et al. Almost all about citrulline in mammals. Amino Acids. 2005;29(3):177–205. doi:10.1007/s00726-005-0235-4 · PubMed
  2. Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. 1999;47(3):261–6. doi:10.1046/j.1365-2125.1999.00883.x · PubMed
  3. Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, 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):51–9. doi:10.1111/j.1365-2125.2007.02990.x · PubMed
  4. Moinard C, Nicolis I, Neveux N, Darquy S, Bénazeth S, Cynober L. 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):855–62. doi:10.1017/S0007114507841110 · PubMed
  5. Gonzalez AM, Trexler ET. Effects of citrulline supplementation on exercise performance in humans: a review of the current literature. J Strength Cond Res. 2020;34(5):1480–95. doi:10.1519/JSC.0000000000003426 · PubMed
  6. Luo P, Li Z, Liu K, Gao W. Effects of L-citrulline supplementation and watermelon intake on arterial stiffness and endothelial function in middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. Front Nutr. 2025;12:1632952. doi:10.3389/fnut.2025.1632952 · PubMed
  7. Gonzalez AM, Spitz RW, Ghigiarelli JJ, Sell KM, Mangine GT. Acute effect of citrulline malate supplementation on upper-body resistance exercise performance in recreationally resistance-trained men. J Strength Cond Res. 2018;32(11):3088–94. doi:10.1519/JSC.0000000000002373 · PubMed
  8. Trexler ET, Persky AM, Ryan ED, Schwartz TA, Stoner L, Smith-Ryan AE. Acute effects of citrulline supplementation on high-intensity strength and power performance: a systematic review and meta-analysis. Sports Med. 2019;49(5):707–18. doi:10.1007/s40279-019-01091-z · PubMed
  9. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215–22. doi:10.1519/JSC.0b013e3181cb28e0 · PubMed
  10. Wang X, Fan X, Chang J, Li H, Zhang X, Zhang Y, et al. Effects of citrulline malate supplementation on exercise performance: a systematic review and three-level meta-analysis. Nutrients. 2026;18(12):1881. doi:10.3390/nu18121881 · PubMed
  11. Viribay A, Fernández-Landa J, Castañeda-Babarro A, Collado PS, Fernández-Lázaro D, Mielgo-Ayuso J. 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 · PubMed
  12. 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. doi:10.1080/15502783.2023.2209056 · PubMed
How this profile was checked

Last reviewed: 2026-10-23. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-23); translation checked on 2026-10-26.

Checked

  • Checked against the abstract: citrulline as masked arginine, conversion in the kidney via ASS, use in urea cycle disorders [1]; n = 10, oral arginine bioavailability ≈ 20% [2]; n = 20, citrulline raises arginine more than arginine (p < 0.01), gut arginase, arginine/ADMA 186 → 278, urinary nitrate 92 → 125, cGMP 38 → 50, FMD not improved by any treatment [3]; n = 8, no side effects, Tmax arginine 1.17–2.29 h, urinary excretion < 5%, saturation of renal conversion [4]; sparse evidence on vasodilation [5]; 8 RCTs, 176 participants, FMD 1.81, PWV not significant [6]; n = 12, no increase in performance, no muscle swelling [7]; 12 studies, 198 participants, SMD 0.20 [8]; n = 41, +52.92%, −40% muscle soreness, stomach complaints 14.63% [9]; 30 RCTs, 644 participants, g 0.16, GRADE low to very low, call for verified composition [10]; 10 studies, SMD 0.15 (p = 0.08) [11]; 9 studies, 158 participants, SMD 0.03 and −0.07 [12].
  • All DOIs checked via Crossref and all PMIDs via PubMed (checking script).

Not verified

  • Legal status of citrulline as a dietary supplement.
  • The unit of the FMD difference in [6] (presumably percentage points) is not given in the abstract.
  • Analyses of the actual citrulline-to-malate ratio of commercially available preparations were not found.
  • Whether citrulline crosses the blood-brain barrier not checked.

No dosages, no sources of supply. This information does not replace medical advice.

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