The Basics
What is L-Citrulline?
L-Citrulline is a non-essential amino acid your body uses to make nitric oxide — the molecule that relaxes and widens blood vessels.
First isolated from watermelon (Citrullus lanatus, the source of its name), L-citrulline isn't built into protein like most amino acids. Instead, it plays a central role in the urea cycle and, importantly, serves as the body's most efficient precursor to L-arginine — the direct fuel for nitric oxide (NO) production. Higher NO means wider blood vessels, improved circulation, and more oxygen and nutrients delivered to working muscle.1
In supplements it appears in two main forms: pure L-citrulline and citrulline malate (L-citrulline bound to malic acid, usually in a 2:1 ratio). Most pre-workout research uses citrulline malate because the malate component also feeds the Krebs cycle and helps buffer ammonia, a contributor to muscular fatigue.5 4 Gauge Pre-Workout uses 6,000 mg of L-Citrulline DL-Malate per serving.
Mechanism
How L-Citrulline works in the body
The path from a scoop of citrulline to a better pump runs through nitric oxide — and, counterintuitively, citrulline does it better than arginine itself.
Once absorbed, L-citrulline travels to the kidneys where it's converted into L-arginine. L-arginine is then used by nitric oxide synthase (NOS) enzymes to produce nitric oxide. NO signals the smooth muscle lining your arteries to relax (vasodilation), increasing blood flow to muscle during exercise.1
Here's the counterintuitive part: oral L-citrulline raises blood arginine levels more effectively than taking L-arginine directly. Swallowed arginine is largely broken down by arginase in the gut and liver before it reaches circulation (first-pass clearance). Citrulline bypasses that, so it delivers arginine to the bloodstream more reliably. In a controlled pharmacokinetic study, citrulline raised plasma arginine in a clear dose-dependent way and improved the arginine-to-ADMA ratio — a marker of NO availability.2
The bottom line
L-Citrulline is essentially a more bioavailable, longer-lasting way to boost nitric oxide than arginine — which is why it has largely replaced arginine in modern pre-workouts.
Benefits At A Glance
What L-Citrulline is studied for
Six research-backed areas where L-citrulline has shown benefits. Select any card to jump to the full evidence.
Key Research Findings
What the literature consistently shows
Plain-language summaries of the strongest, most replicated findings on L-citrulline.
01
Oral L-citrulline raises plasma arginine and nitric oxide more effectively than L-arginine itself, because it escapes first-pass breakdown in the gut and liver.2
02
In resistance-trained men, both L-citrulline and citrulline malate significantly improved upper-body muscular endurance (reps to failure) versus placebo over six weeks.3
03
At 6–8 g, citrulline malate has improved muscular endurance, reduced perceived exertion, and increased nitric oxide markers across multiple RCTs.5
04
Meta-analyses of randomized trials report L-citrulline modestly lowers both brachial and aortic (central) blood pressure.6
05
In a human RCT, men with mild erectile dysfunction saw significantly improved erection hardness on L-citrulline versus placebo — via the same NO pathway that ED medications target downstream.8
Benefit · 01
Blood Flow, Pumps & Nitric Oxide
Bigger pumps through better vasodilation
The benefit most lifters feel first
What the research shows
L-Citrulline's defining action is increasing nitric oxide, which widens blood vessels and increases blood flow to working muscle. A 2023 narrative review in Nutrients examining 2.4–6 g/day of citrulline over 7–16 days found consistent positive effects on nitric oxide synthesis and circulation, and confirmed citrulline outperforms arginine at raising plasma arginine.1 A 2025 RCT in resistance-trained men measured elevated post-exercise nitric oxide metabolites after both citrulline and citrulline malate supplementation.3
Why it matters
More blood flow means more oxygen and nutrient delivery during training, fuller "pumps," and a vascular environment that supports both performance and recovery.
Benefit · 03
Reduced Fatigue & Faster Recovery
Train harder, feel it less
Where the "malate" in citrulline malate earns its place
What the research shows
A 2022 critical review in the European Journal of Applied Physiology noted that beyond boosting nitric oxide, citrulline malate may improve ammonia homeostasis — directly combating the peripheral fatigue associated with high-intensity effort. Malate feeds the Krebs cycle, supporting ATP production and helping clear ammonia that would otherwise accelerate fatigue.5 Across the citrulline literature, reduced ratings of perceived exertion are one of the most consistent findings.1
Why it matters
Lower perceived exertion and better ammonia buffering can translate into more quality reps per session and less day-after soreness.
Benefit · 04
Blood Pressure & Cardiovascular Health
Benefits that reach beyond the gym
The same vasodilation that helps pumps helps your arteries
What the research shows
Because L-citrulline relaxes blood vessels through the nitric oxide pathway, it has been studied for blood pressure. A meta-analysis of randomized controlled trials found that oral L-citrulline significantly reduced both brachial systolic and diastolic blood pressure, and notably lowered aortic (central) systolic pressure — an important marker of cardiovascular load.6 A controlled pharmacokinetic trial similarly showed citrulline improved NO-related signalling and the arginine/ADMA ratio, a measure of endothelial health.2
Important context
Reductions are modest and most relevant as general vascular support, not a treatment for hypertension. If you have high blood pressure or take cardiovascular medication, talk to your doctor before supplementing.
Benefit · 05
Blood Flow & Sexual Health
The same nitric oxide pathway, applied below the belt
An area with surprisingly direct human evidence
What the research shows
An erection is fundamentally a blood-flow event: nitric oxide relaxes penile smooth muscle so the arteries can dilate and fill. This is the same pathway PDE5 inhibitors (such as sildenafil/Viagra) act on — but from the downstream side, while L-citrulline works upstream by supplying more arginine for NO production.11 Men with vascular-origin erectile dysfunction have been shown to have measurably lower arginine and citrulline levels.7
In the pivotal human RCT (Cormio et al.), men with mild ED taking oral L-citrulline saw significantly improved erection hardness versus placebo — 50% reached the hardest score versus 8.3% on placebo, with no adverse events.8 A crossover pilot found citrulline added benefit on top of PDE5 inhibitors,10 and animal work confirmed the vascular mechanism.9 More recently, RigiScan-monitored trials of an L-citrulline + beetroot combination significantly improved nighttime erection quality (a ~33% rise in erection area-under-the-curve), and added to low-dose sildenafil's effect.1213
An honest note
This evidence is promising but still emerging, and 4 Gauge is formulated as an athletic pre-workout — not a treatment for erectile dysfunction. Anyone with sexual-health concerns should speak with a qualified healthcare provider.
Dosage
How much L-Citrulline should you take?
Effective doses depend on your goal and the form. These ranges reflect the doses used in published research.
| Goal | Typical dose | Best form | Timing |
|---|
| Pumps & endurance |
6–8 g |
Citrulline malate |
30–60 min pre-workout |
| Strength & reps |
3–6 g |
L-citrulline or malate |
30–60 min pre-workout |
| Blood pressure / vascular |
3–6 g (e.g., 3 g twice daily) |
L-citrulline |
Daily, ongoing |
| Sexual / blood-flow support |
1.5–6 g |
L-citrulline |
Daily, ongoing |
Good to know
Benefits build with consistent use as nitric-oxide capacity improves. 4 Gauge Pre-Workout's 6,000 mg of citrulline malate sits at the upper, research-backed end for pumps and endurance.5
Safety
Is L-Citrulline safe? Side effects
L-Citrulline is one of the better-tolerated ergogenic ingredients in the research.
Across clinical trials, L-citrulline is generally well-tolerated with few side effects, and human ED research reported no adverse events.8 Unlike high-dose arginine, citrulline rarely causes the gastrointestinal upset associated with arginine supplementation. Because it lowers blood pressure modestly, people taking blood-pressure or erectile-dysfunction medication (especially nitrates or PDE5 inhibitors) should consult a doctor first, as effects on blood pressure could be additive. Pregnant or breastfeeding individuals and anyone with a medical condition should speak with a healthcare provider before use.
In The Formula
L-Citrulline in 4 Gauge Pre-Workout
4 Gauge pairs a clinical-range citrulline dose with a second nitric-oxide pathway for a more complete pump.
Each serving of 4 Gauge Pre-Workout delivers 6,000 mg of L-Citrulline DL-Malate — at the upper end of research-backed dosing for pumps and muscular endurance. Just as importantly, 4 Gauge combines it with 300 mg of Red Beet Root, which supplies dietary nitrate that the body converts to nitric oxide through a separate, non-enzymatic pathway. Together, the two ingredients amplify nitric oxide through complementary routes — a combination that has been directly tested for blood-flow outcomes in human research.12
Feel the difference citrulline makes
Smooth, sustained energy and serious pumps — powered by a 6,000 mg citrulline malate dose and a complementary beet-root nitric-oxide pathway.
- 6,000 mg citrulline malate
- Dual nitric-oxide pathways
- No proprietary blends
- Smooth energy, no crash
Continue Your Research
Keep exploring the Research Hub
More evidence-based ingredient and topic deep dives from the 4 Gauge Research Hub.
About the Author
Who wrote and reviewed this page
Author & Reviewer
Connor Southworth
Founder, 4 Gauge
Connor Southworth is the founder of 4 Gauge and has spent years researching, formulating and manufacturing premium nutritional supplements. He personally oversees product development and ingredient selection, with a focus on evidence-based formulations designed to support performance, recovery and long-term health.
10+ yrsIn nutrition
Evidence-ledFocus
June 2026Last reviewed
June 2027Next review
FAQ
L-Citrulline: common questions
What are the main benefits of L-Citrulline?
L-Citrulline boosts nitric oxide and blood flow, which research links to better muscle pumps, improved muscular endurance, reduced perceived exertion and soreness, and modest reductions in blood pressure. The same blood-flow mechanism has also shown benefits for erectile function in men with mild ED.
Is L-Citrulline or Citrulline Malate better?
Both raise nitric oxide and, in a head-to-head RCT, both improved muscular endurance with no significant difference. Citrulline malate adds malic acid, which helps buffer ammonia and is the form used in most pre-workout research, so it's often preferred for training. Pure L-citrulline is slightly more concentrated per gram and common in blood-pressure studies.
How much L-Citrulline should I take?
For pumps and endurance, 6–8 g of citrulline malate (or 3–6 g of pure L-citrulline) about 30–60 minutes before training is the research-backed range. For blood-pressure or general vascular support, 3–6 g daily on an ongoing basis is typical. 4 Gauge Pre-Workout provides 6,000 mg of citrulline malate per serving.
How long does L-Citrulline take to work?
Acute effects on blood flow occur within roughly an hour of a single dose, which is why it's taken pre-workout. Endurance, blood-pressure and vascular benefits build with consistent daily use over days to weeks as nitric-oxide capacity improves.
Does L-Citrulline have side effects?
It's one of the better-tolerated ergogenic ingredients and rarely causes the stomach upset linked to high-dose arginine. Because it can modestly lower blood pressure, anyone taking blood-pressure medication, nitrates or PDE5 inhibitors should consult a doctor first.
Sources & References
The research behind L-Citrulline
Grouped by topic. Human RCTs, meta-analyses and pharmacokinetic studies are weighted above mechanistic or animal data.
01 · TopicMechanism & Pharmacokinetics
- 1.Park H-Y, et al. "Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review." Nutrients, 2023;15(5):1268. PMC10005484
- 2.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. PMC2291275
02 · TopicExercise Performance & Endurance
- 3.Bayat D, et al. "Changes in resistance training performance after six weeks of supplementation with L-citrulline vs. L-citrulline DL-malate." J Int Soc Sports Nutr, 2025. View source
- 4.Nobari H, et al. "Overview of mechanisms related to citrulline malate supplementation and HIIT on sports performance." Heliyon, 2025;11(4):e42649. PMC11876876
- 5.Bridge CA, et al. "A critical review of citrulline malate supplementation and exercise performance." Eur J Appl Physiol, 2022;122:21–36. PMC8571142
03 · TopicBlood Pressure & Cardiovascular
- 6."Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials." Nutr Metab (Lond), 2019. PMC6933755
04 · TopicBlood Flow & Sexual Health
- 7.Barassi A, et al. "Levels of L-arginine and L-citrulline in patients with erectile dysfunction of different etiology." Andrology, 2017;5(2):256–261. doi:10.1111/andr.12293
- 8.Cormio L, et al. "Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction." Urology, 2011;77(1):119–122. View source
- 9.Shiota A, et al. "Oral L-citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction." J Sex Med, 2013;10(10):2423–2429. View source
- 10.Iwasa A, et al. "Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With PDE5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study." Urol Int, 2018;101(3):286–291. PMC6302103
- 11.Argiolas A, Melis MR. "Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System." Biomolecules, 2021;11(12):1866. View source
- 12.Brandeis J, Justin B. "L-Citrulline and Beet Root Supplement Improves Nighttime Erections." J Sex Med, 2024;21(Suppl 1) [abstract]. View source
- 13.Brandeis J, et al. "Combining a Nitric Oxide Boosting Dietary Supplement With Sildenafil Improves Nighttime Erections More Than Sildenafil Alone." J Sex Med, 2025;22(Suppl 1) [abstract]. View source
