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Nootropics>Amino acids & derivatives>L-Citrulline
Amino acids & derivatives

L-Citrulline

L-citrulline ((2S)-2-amino-5-(carbamoylamino)pentanoic acid)

L-Citrulline is a nonessential amino acid and arginine precursor. Human research is mainly vascular and exercise-related: high-intensity strength and power findings are small or mixed, while a 2023 review found no significant acute endurance benefit in young healthy adults. Compare pure L-citrulline with citrulline malate by actual citrulline grams, malate ratio, study context, tolerance, and like-for-like price.

Physical PerformanceEnduranceRecovery SupportNitric Oxide RelatedBlood Flow SupportFood DerivedBioavailability Sensitive
Updated August 2026/6 min read/12 citations
Reviewed by the NootropicsIndex editorial team.Method: prioritize cited human research and official safety or regulatory sources; compare retailer-listed prices without endorsing products.Affiliate disclosure
01

What is it?

What L-Citrulline is

7

L-Citrulline is a nonessential amino acid and urea-cycle intermediate. Human pharmacokinetic research shows that oral L-citrulline raises circulating citrulline and can raise plasma arginine.

Compare the ingredient amount6
Compare the label's L-citrulline amount with the total citrulline-malate serving. The malate ratio changes the amount of citrulline supplied.

High-intensity strength and power evidence

4

A 2019 meta-analysis of acute high-intensity strength and power trials found at most a small pooled signal. The result should not be read as a guaranteed performance outcome.

Vascular findings are context-specific

2

A 2025 meta-analysis of middle-aged and older adults pooled L-citrulline and watermelon studies and reported modest resting blood-pressure changes. Its pooled estimates were highly heterogeneous, so results should not be generalized across populations or interventions.

Endurance evidence in young healthy adults3
A 2023 systematic review and meta-analysis of nine trials in 158 young healthy adults found no significant acute endurance-performance benefit. That result does not establish outcomes in other populations or formulations.
02

Names, aliases and forms

Common NamesL-citrulline; citrulline; citrulline malate; citrulline DL-malate
Chemical Names(2S)-2-amino-5-(carbamoylamino)pentanoic acid; N5-carbamoyl-L-ornithine
Cas Number372-75-8
Molecular FormulaC6H13N3O3
03

Mechanisms of action

Arginine-precursor pathway

7

L-Citrulline enters the intestinal-renal arginine-citrulline pathway. It raises citrulline and arginine exposure, but a concentration change does not by itself establish a practical performance outcome.

04

Potential effects and evidence map

L-Citrulline raises circulating citrulline and arginine. In acute high-intensity strength and power research, pooled effects are small at most; a 2023 meta-analysis found no significant acute endurance benefit in young healthy adults. A 2025 review of middle-aged and older adults reported modest resting blood-pressure changes, but pooled estimates were highly heterogeneous across interventions and populations. Pure L-citrulline and citrulline malate should not be regarded as gram-for-gram equivalents.

Effect domainMagnitudeGrade
Physical energy / endurance4
AcuteConfidence: Medium

In acute high-intensity strength and power research, L-citrulline and citrulline malate showed at most a small pooled effect; individual outcomes should not be presented as guaranteed.

Note This rating is limited to the acute high-intensity strength and power evidence reviewed by Trexler et al.; it does not cover endurance or all citrulline-malate outcomes.

2/5
C
05

Typical dosages and timing

Typical
3-9 g/day
Not a recommendation
Lower bound
3 g/day
Profile value
Upper bound
9 g/day
Profile value
common acute protocol68 g

A single 8 g citrulline-malate dose is common in acute exercise studies. Its citrulline amount depends on the stated ratio and batch composition.

06

Timing & effect horizon

Effect horizonAcute + cumulative
AcuteCumulative
Plasma arginine peak7Acute
1.2-2.3 h
Study window10Cumulative
1-17 weeks
Repeated-study context10

A pure L-citrulline blood-pressure meta-analysis included 3-9 g/day interventions lasting 1-17 weeks. Those study windows are not a recommended cycle.

Plasma arginine response7

In eight healthy men given 2-15 g L-citrulline, plasma arginine peak time was 1.17-2.29 hours. This is a concentration finding, not an established effect onset or schedule recommendation.

07

Safety, side effects and risk profile

Blood-pressure context2
Blood-pressure outcomes differed across studies and populations. People with lower baseline blood pressure may want to account for that context before adding L-citrulline.
Pregnancy and lactation evidence gap11
The short-term tolerance trial was conducted in healthy adult men. It does not establish safety in pregnancy or lactation; pregnancy-focused L-citrulline research is a separate emerging clinical context.
Cardiovascular caution2
Confidence: Medium

Blood-pressure changes reported in selected study populations may be relevant for people with lower baseline blood pressure.

Note This is a context-specific caution, not the base risk for a generally healthy adult using ordinary oral amounts; the pooled estimates were heterogeneous.

2/5
C
GI discomfort8
Confidence: Medium

Tolerance can differ by dose and formulation; a four-week trial in healthy adult men reported no study-related adverse events through 24 g/day.

Note The trial does not predict individual tolerance or longer-term experience.

1/5
C
Pregnancy / lactation caution11
Confidence: Medium

Short-term healthy-adult male data do not establish safety in pregnancy or lactation.

Note Pregnancy-focused L-citrulline research is a separate emerging clinical context, not a general sports-supplement safety conclusion.

1/5
D
healthy adult men8

In a four-week dose-ranging study in healthy adult men, citrulline at 6-24 g/day was tolerated without study-related adverse events. That finding does not predict individual tolerance or longer-term experience.

08

Interactions and cautions

no ingredient-specific estimate listed12

The cited L-citrulline trials and reviews do not quantify interactions with individual medicines. This page therefore does not list a confirmed L-citrulline medicine interaction; general supplement-medicine interaction guidance cannot establish ingredient-specific effects.

09

Legal and regulatory status

FDA; as of 20269

For L-citrulline products marketed as dietary supplements in the United States, FDA's general dietary-supplement framework applies. As of 2026, FDA does not pre-approve dietary supplements or their labeling for safety and effectiveness before sale; makers remain responsible for lawful safety and labeling. This is a U.S. regulatory note, not product-specific approval or legal advice.

10

How it compares

Pure L-citrulline1

This is the free amino acid. Compare products by their listed L-citrulline grams.

Citrulline malate6

Citrulline malate combines citrulline with malate. A serving's total weight is not the same as its L-citrulline amount; check the ratio and label details.

11

Practical buying and quality notes

  • For powders, compare actual L-citrulline grams, the citrulline-malate ratio, serving size, and independently verifiable testing or certificates. Normalize price only among comparable forms and quantities; a low per-gram citrulline-malate price is not the same as a pure L-citrulline price.6
12

FAQ

Does L-citrulline improve endurance?

3

A 2023 meta-analysis found no significant acute endurance-performance benefit in young healthy adults. That evidence does not settle other outcomes, populations, or formulations.

What is the difference between L-citrulline and citrulline malate?

6

L-citrulline is the amino acid. Citrulline malate combines citrulline with malate, so total serving weight should not be equated with the L-citrulline amount.

How should doses be compared?

6

Do not equate pure L-citrulline and citrulline malate by total grams. A single 8 g citrulline-malate protocol is common in acute exercise studies, but the actual citrulline amount depends on the stated ratio and batch composition.

Is there an established cycle?

8

A four-week healthy-adult tolerance trial is not evidence for a required cycle. This profile does not present a cycling schedule.

13

References

  1. PubChem Compound Summary for L-citrulline. National Center for Biotechnology Information.
  2. Luo P, Chen J, Liu K, Zhang J. Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults? A systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN. 2025.
  3. Harnden CS, Agu J, Gascoyne T. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. Journal of the International Society of Sports Nutrition. 2023.
  4. 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 Medicine. 2019.
  5. 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. Journal of Dietary Supplements. 2022.
  6. Gough LA, Sparks SA, McNaughton LR, Higgins MF. A critical review of citrulline malate supplementation and exercise performance. European Journal of Applied Physiology. 2021.
  7. Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. British Journal of Nutrition. 2008.
  8. Miura N, Morishita K, Yasuda T, Akiduki S, Matsumoto H. Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults. Amino Acids. 2023;55(3):299-311.
  9. FDA 101: Dietary Supplements. U.S. Food and Drug Administration. Accessed 2026.
  10. Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B. Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis. Avicenna Journal of Phytomedicine. 2019;9(1):10-20.
  11. Collins-Smith A, Jain S, Jain S. L-Citrulline in Maternal-Fetal and Neonatal Health: Metabolic Mechanisms and Emerging Therapeutic Applications. Nutrients. 2026;18(12):1923.
  12. How Medications and Supplements Can Interact. National Center for Complementary and Integrative Health. Accessed 2026.
Note

This page is informational and summarizes available evidence. It is not medical advice, a recommendation, or a substitute for guidance from a qualified clinician.