At a glance
- Citrulline is an amino acid made from glutamine in the body and also found in watermelon; about 80% of it is converted to arginine in the kidneys. [1]
- In 20 healthy volunteers, oral citrulline raised plasma arginine more effectively than arginine itself; this is a blood-level result. [2]
- A small effect was found in the 12-study meta-analysis for acute high-intensity strength and power (SMD 0.20; 95% CI 0.01–0.39). [3]
- NIH ODS finds research support for performance limited and conflicting; the safety of use lasting months has not been adequately evaluated. [1]
- This guide does not set personal doses.
What is citrulline and what does it do in the body?
Citrulline is a nonessential amino acid: it is made in the body mostly from glutamine and is also obtained from food. The best-known food source is watermelon; according to NIH ODS, 1 cup (U.S. cup, ≈240 mL) of diced seedless watermelon contains about 365 mg of citrulline. About 80% of the body’s citrulline is converted in the kidneys to another amino acid, arginine; vasodilating nitric oxide is in turn made from arginine. This chain is the basis of the assumption that citrulline may be ergogenic (performance-enhancing). NIH ODS also states that citrulline is absorbed from the gut more than arginine, so it may be a more efficient way of raising blood arginine levels. [1]
This relationship was examined in a randomized, double-blind, placebo-controlled crossover study: 20 healthy volunteers received placebo, citrulline, and arginine in six different dose regimens. After one week, citrulline raised the area under the curve (AUC) and peak level (Cmax) of plasma arginine more effectively than arginine in a dose-dependent manner. At the highest citrulline dose (3 g twice a day), the arginine/ADMA ratio rose from 186 ± 8 to 278 ± 14 (95% CI 66–121), and urinary nitrate and cGMP levels increased. No intervention improved flow-mediated dilation (FMD) from baseline. [2]
How does citrulline affect blood arginine levels?
The result of the study above is limited to blood levels and urinary markers; no health or performance outcome was measured. The 2020 review by Gonzalez and Trexler states that oral citrulline and citrulline malate raise plasma citrulline and arginine levels and total nitrate/nitrite levels, but that the evidence supporting an acute increase in blood flow and improvement in muscle tissue perfusion is “scarce and inconsistent.” [4]
What forms are available, and what does the “2:1” label mean?
Supplement products contain citrulline or citrulline malate. According to NIH ODS, most studies used citrulline malate, a combination of citrulline with malic acid; malic acid is a Krebs cycle intermediate and is assumed to be able to increase energy production. Citrulline malate is 56.64% citrulline by weight; that is, 1 g of citrulline malate provides 566 mg of citrulline. No study examines whether products labeled “citrulline malate 2:1” or “tri-citrulline malate” are superior to standard citrulline or citrulline malate. [1] This ratio matters: “8 g of citrulline malate” in studies does not mean 8 g of citrulline; with the 56.64% ratio NIH gives, it corresponds to about 4.5 g of citrulline (calculation).
Is it possible to reach study amounts with watermelon?
A comparison can be made using the 56.64% ratio from NIH ODS and the watermelon value: the 8 g of citrulline malate used in studies corresponds to about 4.5 g of citrulline, which is the amount of citrulline in about 12 cups (U.S. cup, ≈240 mL) of diced seedless watermelon (calculation; NIH values were used). [1] This comparison is not a recommendation but an indication that supplement studies rest on a scale far above the amount obtained from food.
Does citrulline improve athletic performance?
NIH ODS finds support for citrulline as a performance enhancer “at best limited and conflicting”; the published studies have heterogeneous designs and lasted 1–16 days. [1]
The 2019 systematic review and meta-analysis by Trexler and colleagues examined the effect of acute citrulline supplementation in healthy women and men on high-intensity strength and power outcomes, covering sprints of 30 seconds or less or resistance-training sets. Studies without placebo, conducted in clinical populations, using less than 3 g of citrulline, giving it less than 30 minutes before exercise, or combining citrulline with other ingredients such as creatine, caffeine, and nitrate were excluded. 12 studies (13 independent samples, 198 participants) entered the analysis; heterogeneity was low (Q=6.9; p=0.86; I² 0%). Citrulline showed a small significant benefit relative to placebo: standardized mean difference (Hedges g) 0.20 (95% CI 0.01–0.39; p=0.036). The authors state that the effect is small and that each study’s confidence interval included zero; they add that the result may be meaningful for elite athletes, for whom competition outcomes are determined by small margins. [3]
The Gonzalez and Trexler review, on the other hand, says that there are studies reporting increased performance and recovery, but that additional studies are needed to clarify the mechanism of the effect and to measure blood flow markers. [4] According to NIH ODS, the studies reviewed lasted 1–16 days; no performance outcome has been measured for training periods lasting months. [1]
Does citrulline reduce muscle soreness?
In the study by Pérez-Guisado and Jakeman, 41 men performed two consecutive chest-training protocols (16 sets) in a randomized, double-blind, 2-period crossover design; 8 g of citrulline malate was used in one and placebo in the other. Repetitions increased significantly from placebo to citrulline malate starting in the third set (p < 0.0001); the authors reported 52.92% more repetitions in the last set and a 40% reduction in muscle soreness at 24 and 48 hours. The only side effect reported was stomach upset in 14.63% of participants. [5] NIH ODS reports the same study as one conducted with 41 healthy male weightlifters aged 22–37, and states that in another randomized study of 17 young healthy women and men given citrulline without malate (3 g before the test or 9 g over 24 hours), those taking citrulline performed worse than those taking placebo in an incremental fast treadmill test. [1] The positive result in a single study therefore sits within a conflicting picture.
Does citrulline work in endurance sports?
In a meta-analysis examining foods rich in citrulline (only 3 of 118 studies were citrulline studies), no effect on exercise performance was found after consumption of citrulline-containing foods (SMD −0.03; p=0.24). This result covers food sources, not citrulline supplementation, and the subgroup is very small; even so, no positive effect has been shown for endurance. [6]
Does citrulline lower blood pressure?
In a 2025 meta-analysis, 15 RCTs (24 datasets, 415 middle-aged and older participants) were combined; when L-citrulline supplementation and watermelon consumption were evaluated together, systolic blood pressure fell 4.02 mmHg (95% CI −6.54 to −1.50) and diastolic 2.54 mmHg (−4.27 to −0.81). In the subgroup where L-citrulline and L-arginine were given together, the reduction was larger (systolic −10.44 mmHg). [7] Because this analysis pooled supplement and food studies, it is hard to draw conclusions for pure citrulline supplementation. A previously published citrulline–blood pressure meta-analysis (J Hum Hypertens) was retracted in 2021; the results of that review are not considered valid. [9]
Does citrulline help erection problems?
In the single-blind study by Cormio and colleagues, 24 men with mild erectile dysfunction and an erection hardness score of 3 (mean age 56.5 ± 9.8) received placebo for one month, then 1.5 g of L-citrulline per day for one month. The hardness score rose from 3 to 4 (normal) in 2 men (8.3%) in the placebo month and 12 men (50%) in the citrulline month (p < 0.01); monthly intercourse count rose from 1.37 ± 0.93 to 2.3 ± 1.37. The authors state that in the short term, citrulline is less effective than phosphodiesterase-5 inhibitors and that more studies are needed. [8] Because the design was sequential (placebo always in the first month), an order effect cannot be excluded.
Is citrulline safe?
According to NIH ODS, the safety of citrulline has not been adequately evaluated, particularly for supplement use lasting months. 6 of 41 weightlifters (14.6%) reported stomach upset after citrulline malate. In short studies in non-athletes, no adverse effects were reported with up to 6 g per day for 4 weeks and 1.35 g per day for 6 weeks. [1] These durations do not cover use measured in months; absence of data does not mean harmlessness.
Is citrulline different from arginine, and which has better evidence?
The two amino acids are in the same nitric oxide pathway; arginine is the direct precursor, and citrulline is the precursor that is converted to arginine. In terms of blood level, citrulline came out ahead (plasma arginine AUC and Cmax in 20 volunteers). [2] For performance, NIH ODS finds support for both limited or scant; details and the mortality signal in the post–heart attack study are given separately on the arginine page. [1] This page does not declare either substance superior to the other: a blood-level result is not a substitute for evidence of performance or clinical benefit.
What is known about product labels and reliability?
NIH ODS reports that many sports supplements contain multiple ingredients that have not been adequately tested together, and that products marketed for bodybuilding are among those most often adulterated with undeclared anabolic steroids and prescription drugs (citing the FDA). Independent third-party certification programs can verify that contents match the label and that many prohibited substances are absent; the risk of prohibited substances can also mean doping sanctions for athletes. [1] These points are not specific to citrulline and apply to all sports supplements.
Citrulline supplements in Türkiye
Approval from the Ministry of Agriculture and Forestry is mandatory for every dietary supplement to be marketed in Türkiye. [10] In the Restricted Substances List (last updated September 21, 2026), the L-citrulline row is of chemical synthesis origin and carries an upper limit of 1,000 mg/day in the age 11 and over column (published March 8, 2016, updated September 27, 2017); no value is entered in the 4–10 year columns. There is no separate row named “citrulline malate” in the list. [11]
The amounts used in studies are not on the same scale as this limit: the meta-analysis’s inclusion criterion was at least 3 g of citrulline, 3 g twice a day was tested in the blood-level study, and 1.5 g per day was used in the erection study. [3] [2] [8] These are above the list limit; study doses cannot be taken as a criterion for a product approved in Türkiye.
Evidence table: claim, population, and limits
| Claim | Population studied | Limit |
|---|---|---|
| Increases acute power and strength | 12 studies, 198 healthy adults | Small effect (SMD 0.20); each study’s CI includes zero. [3] |
| Reduces muscle soreness | 41 men, single dose, crossover | Single study; NIH ODS gives a conflicting example. [5] [1] |
| Improves endurance | 3 studies (citrulline-containing foods) | No effect (SMD −0.03). [6] |
| Lowers blood pressure | 15 RCTs, 415 middle-aged/older | Supplement and watermelon mixed; an earlier meta-analysis was retracted. [7] [9] |
| Improves erection | 24 men, mild ED | Sequential design, not randomized. [8] |
| Raises arginine level | 20 healthy volunteers | Biomarker; FMD did not change. [2] |
This guide does not recommend personal doses or treatment; in the presence of an erection problem, high blood pressure, or regular medication use, the decision depends on individual clinical assessment.
What does the evidence say?
What it does and does not affectLimited or insufficient evidence
- CAcute high-intensity strength and power — small effectIn 12 studies (13 samples, 198 participants), SMD 0.20 (95% CI 0.01–0.39; p=0.036); the effect is small, and each study's CI includes zero. For studies meeting the criteria, intake of ≥3 g of citrulline at least 30 minutes before exercise was required.
- CBlood pressure — small reduction (mixed population)In 15 RCTs (415 participants, middle-aged and older), when citrulline supplementation and watermelon were evaluated together, systolic blood pressure fell 4.02 mmHg; methods and population are mixed, and an earlier citrulline–blood pressure meta-analysis was retracted.
- CBlood arginine level and nitric oxide markers (biomarker)In 20 healthy volunteers, the highest citrulline dose raised the arginine/ADMA ratio from 186 to 278 and increased urinary nitrate and cGMP; no intervention improved flow-mediated dilation (FMD) from baseline.
- DPost-exercise muscle soreness (single-dose study)In a crossover study of 41 men, muscle soreness fell about 40% at 24 and 48 hours after a single dose of citrulline malate (reported by the authors); NIH ODS finds the example studies conflicting; a single study.
- DMild erectile dysfunction (24 men, single-blind)In a sequential placebo-then-citrulline design, the hardness score rose from 3 to 4 in 2 men (8.3%) in the placebo month and 12 men (50%) in the citrulline month; not randomized, single-center, and small.
What do the A–E grades mean?
The letter describes the strength of evidence for a specific claim, not the size of the benefit or a usage recommendation. E does not mean ineffectiveness has been proven.
- AStrong
- Established physiology (e.g. correcting a deficiency) or strong, consistent, direct human studies
- BModerate
- Supportive human evidence; small effect or some limitations
- CLimited
- A single randomised trial, mixed results or low-certainty human findings
- DInsufficient
- Small, uncontrolled or indirect evidence; not enough to judge
- ENo benefit shown / not studied in humans
- No benefit shown for the claim, or only animal or cell data exist
These grades are Half-Life Journal’s editorial evidence summary; they are not a formal GRADE rating or independent medical approval.
The letter shows evidence strength; it is not a score for positive effect or a usage recommendation.
Frequently asked questions
What does citrulline do?
Citrulline is an amino acid made from glutamine in the body and found in foods such as watermelon; about 80% of it is converted to arginine in the kidneys. Supplementation raises blood arginine levels, but according to NIH ODS the evidence for exercise performance is limited and conflicting.
Does citrulline improve performance?
In a 12-study meta-analysis (198 participants) examining acute high-intensity strength and power outcomes, a small effect was reported (SMD 0.20; 95% CI 0.01–0.39); each study's confidence interval included zero. No effect of citrulline-containing foods was found for endurance (SMD −0.03).
What is the difference between citrulline and arginine?
Citrulline is converted to arginine in the body; in a crossover study of 20 healthy volunteers, it raised plasma arginine more effectively than arginine itself. This is a blood-level result; it does not mean performance or clinical benefit.
Does citrulline help erection problems?
In a single, small, single-blind study of 24 men with mild erectile dysfunction, one month of placebo was followed by one month of citrulline; the hardness score improved in 8.3% of men in the placebo month and 50% in the citrulline month. The study is not randomized, and the authors state that citrulline is less effective than drugs.
Is there a limit for citrulline in Türkiye?
The Ministry of Agriculture and Forestry's Restricted Substances List lists a maximum of 1,000 mg/day of L-citrulline for age 11 and over. The list has no separate row for citrulline malate.
Sources
- Guideline / review NIH ODS — Dietary Supplements for Exercise and Athletic Performance (Health Professional Fact Sheet)Back to text ↑
- RCT Schwedhelm et al. — Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism (Br J Clin Pharmacol) (2008)Back to text ↑
- Trexler et al. — Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis (Sports Med) (2019)Back to text ↑
- Guideline / review Gonzalez ve Trexler — Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature (J Strength Cond Res) (2020)Back to text ↑
- RCT Pérez-Guisado ve Jakeman — Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness (J Strength Cond Res) (2010)Back to text ↑
- d’Unienville et al. — Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials (J Int Soc Sports Nutr) (2021)Back to text ↑
- Luo et al. — 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 (Clin Nutr ESPEN) (2025)Back to text ↑
- Human study Cormio et al. — Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction (Urology) (2011)Back to text ↑
- Source Retraction Note: Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials (J Hum Hypertens) (2021)Back to text ↑
- Institution T.C. Tarım ve Orman Bakanlığı, Ankara İl Müdürlüğü — Takviye Edici Gıdalar Onay Başvuru İşlemleri (2026)Back to text ↑
- Institution T.C. Tarım ve Orman Bakanlığı — Takviye Edici Gıdalar Kısıtlı Maddeler Listesi (son güncelleme 21/09/2026) (2026)Back to text ↑
Method: Institutional clinical guidance and relevant studies were compared. Each finding is presented with its population, outcome, sources and limitations. Independent medical review has not yet been completed.
Updated
This content is for information only and is not medical advice. It does not recommend doses, products or vendors. Talk to your clinician before making any health decision.


