Citrulline: Uses, Benefits, Dosage, and Side Effects

L-citrulline, or just citrulline, is a non-essential amino acid that the body converts into L-arginine and nitric oxide, which helps improve blood flow and vascular health. It is often used in supplement form to enhance athletic performance, reduce muscle fatigue, and support cardiovascular function.

Table of Contents

Outcome Summary

This tier list summarizes the primary outcomes of citrulline supplementation and grades them from A (best) to E (worst), based on up-to-date scientific evidence.

A: Best in class for that particular outcome. Recommended for practically everyone.
B: Worth the money for most people and backed by scientific evidence to provide significant positive effects.
C: Might be worth trying, but the effects are small to modest, or the research is limited in size and scope.
D: Generally ineffective, although not harmful.
E: Negative or even harmful effects.

You can find references in the detailed research review of each outcome below.

Effect	Tier (A = best, E = worst)	Summary
Strength	D	There is little evidence that L-citrulline improves maximum strength. However, it might have a small effect in high-level athletes.
Muscle Growth	D	One study found slightly better gains after four weeks compared to a placebo.
Body Fat	D	There is limited direct evidence to support L-citrulline as a significant weight loss or fat loss supplement. However, its indirect benefits in improving exercise performance, recovery, and possibly insulin sensitivity could help support a fat-loss regimen when combined with a calorie-controlled diet and regular exercise.
Athletic Performance	C	Citrulline has little to no benefits for endurance/aerobic performance. It might increase repetition performance during strength training.
Hormones	D	Citrulline does not affect anabolic hormones at rest, although it might increase growth hormone levels after exercise.
Improved Blood Flow	B	Citrulline moderately boosts exercise muscle blood flow in older adults but might not be as effective for young and healthy athletes.

What Is Citrulline?

Citrulline is a naturally occurring amino acid that plays a significant role in several physiological processes in the body. It is especially involved in cardiovascular health, exercise performance, and muscle recovery.

Citrulline likely does not directly contribute to protein synthesis (except possibly if you eat a very low-protein diet,) although it improves nitrogen balance. It acts as a precursor for arginine, which plays a key role in nitric oxide (NO) production. It is also crucial in the urea cycle, which helps detoxify ammonia, a waste product of protein metabolism.

Citrulline is naturally found in some foods, including watermelon (the richest natural source, especially in the rind), cucumbers, pumpkins, and gourds. The name citrulline comes from Citrullus lanatus, the Latin word for watermelon.

References: ¹ ²

Physiological Roles of Citrulline and Citrulline Supplements

There are two main forms of citrulline supplements:

L-citrulline: Pure form of citrulline.
Citrulline malate: A combination of citrulline and malic acid, often marketed for enhanced athletic performance due to its potential ability to aid in energy production.

L-Citrulline

Citrulline plays several important physiological roles in the body:

Nitric Oxide Metabolism

Citrulline is involved in the urea cycle, where it is converted into arginine, a precursor for nitric oxide (NO). Nitric oxide is a vasodilator that helps relax and widen the blood vessels, improving blood flow.

The enhanced blood flow is thought to boost nutrient and oxygen delivery to muscles, which is why citrulline is often used in pre-workout supplements for better endurance and muscle pumps.

However, there is little consistent evidence that citrulline supplementation increases vasodilation after ingestion.

Ammonia Clearance

Citrulline helps remove ammonia, a toxic byproduct of protein metabolism, from the body via the urea cycle.

Reducing fatigue caused by ammonia buildup could improve metabolic efficiency during exercise, particularly in prolonged physical activities.

Enhanced Exercise Performance

Citrulline could enhance aerobic and anaerobic performance, although most studies do not support this theory or show, at best, a small effect.

Increased blood flow after citrulline supplementation may also help reduce post-exercise muscle soreness and promote faster recovery.

Cardiovascular Health

L-citrulline supports cardiovascular health mainly by boosting the production of nitric oxide, which helps relax blood vessels. This so-called vasodilation improves blood flow, reduces blood pressure levels, and improves heart health by protecting against issues like hypertension and atherosclerosis (the buildup of plaque in the arteries).

Citrulline is more effective than arginine for increasing l-arginine levels because it is not broken down in the digestive tract. More of it is converted into arginine in the body, which then leads to greater nitric oxide production.

Citrulline also has antioxidant and anti-inflammatory properties that reduce the oxidative stress and inflammation often linked to cardiovascular disease.

Muscle Protein Synthesis

While citrulline doesn’t directly trigger muscle protein synthesis like essential amino acids (e.g., leucine), it modulates the conditions that support it, especially under challenging conditions like low-protein diets.

Citrulline stimulates the so-called mTORC1 pathway, which regulates how the body builds proteins. This pathway triggers the activation of several proteins essential for muscle protein creation.

Citrulline also helps the body better allocate energy towards building muscle proteins, which could explain why it boosts protein synthesis, particularly when other resources like amino acids are scarce.

Citrulline Malate

When citrulline is combined with malate (malic acid), it creates citrulline malate, which provides additional benefits:

Energy Production

Malate plays a role in the Krebs cycle (citric acid cycle). It helps increase the production of ATP (the primary energy currency in cells,) which could improve stamina, reduce fatigue, and delay exhaustion by enhancing the body’s energy production efficiency.

Lactic Acid Buffering

The combination of citrulline and malate is thought to help buffer lactate buildup in muscles, which is a major cause of the burning sensation during strenuous exercise.

Synergistic Effects on Exercise Performance

Citrulline malate has been theorized to improve performance in high-intensity activities and promote quicker recovery between sets during resistance training.

The combination of increased blood flow (from citrulline) and enhanced energy production (from malate) creates a synergistic effect, which might lead to better endurance and strength performance.

Though these mechanisms are promising, more research is needed to fully confirm their effectiveness in humans. Most of the supporting studies are based on animal models or theoretical frameworks.

References: ³ ⁴ ⁵

Does Citrulline Increase Max Strength and Power?

Citrulline could help strength and power performance by improving blood flow to muscles through nitric oxide production, removing ammonia (a waste product linked to muscle fatigue), boosting ATP (energy) production by enhancing the TCA cycle and aiding oxygen and nutrient delivery.

Three recent scientific reviews and meta-analyses examine the effects of citrulline and citrulline malate supplementation on strength and power outcomes.³ ⁶ ⁷

The results show a small positive effect of citrulline supplementation, with a modest improvement in strength and power compared to a placebo. Strength tasks (the ability to exert force against resistance) tend to benefit more from citrulline supplementation than power tasks (the ability to exert force quickly).

However, the improvements are very minor. While it might be helpful for elite athletes, where even small improvements can make a difference, it likely doesn’t provide much benefit for increasing strength in the general population, including trained people.

Some studies report minor improvements in endurance and repetitions to failure during strength exercises (like bench press or leg press) in trained individuals. Other studies show no effect, particularly in power-based movements, and the benefits seem limited when using very high-intensity training protocols.

In short, citrulline and citrulline malate could slightly improve muscular endurance and reduce fatigue, but their effect on strength and power output is inconclusive. In addition, the available studies are small and underpowered. They may have some application in specific contexts, particularly in high-level athletes. However, its effects on strength and power are likely negligible for the general population.

Does Citrulline Increase Repetition Performance?

One of the purported benefits of citrulline supplementation is improved repetition performance, meaning you can do more reps per set or workout with a particular load.

Citrulline malate has been shown to increase repetition performance in some studies.³ For example, one study demonstrated that an acute dose of 8g of citrulline malate taken 1 hour before exercise improved repetitions to failure in the barbell bench press. Other studies have also found that citrulline malate increased repetitions to failure during exercises like leg press, hack squat, and bodyweight exercises like chin-ups and push-ups.

However, results have been mixed. Some studies found no improvement in repetitions to failure during exercises like barbell curls or leg curls using German Volume Training protocols (you perform 10 sets of 10 repetitions of a single exercise with the same weight).

These outcome differences may be due to factors like the citrulline-to-malate ratio or the exercise protocols’ reliability.

In addition to earlier findings, a 2024 study – too recent to be included in any comparative analyses – is worth mentioning.⁸

The study was a counterbalanced, randomized, double-blind, placebo cross-over trial. That means the researchers set up the study so that chance decided who got what treatment, and nobody knew who was getting which treatment at any time. Everyone tried all the treatments at some point and the order was mixed up to ensure it was fair.

They recruited 11 trained men and had them follow a German Volume Training protocol involving 10 sets of 10 maximal knee extensions. The participants took an 8g dose of citrulline malate (CM) daily for four days. Half the time, they took CM; the other half, they took a placebo without them or the researchers knowing which they were getting.

Participants on CM were able to perform more total repetitions (68.1 on average) compared to the placebo group (54.9,) suggesting that CM might help complete more total work in a training session.
While CM increased the total number of reps, it did not improve muscular endurance across individual sets. In other words, it didn’t help the athletes maintain strength as they got tired over time.
There were no notable differences in muscle strength or recovery speed between those taking CM and the placebo, and CM did not reduce overall muscle soreness compared to the placebo. In addition, the study found no major differences in blood lactate (a marker of muscle fatigue) or creatine kinase (a marker of muscle damage) between the two groups.

In short, according to scientific reviews and more recent research, citrulline malate may enhance repetition performance, particularly in certain training settings.

However, as several studies have shown no benefits, the results might vary depending on the study design and supplement formulation, and further research is needed to determine the ideal conditions and dosage for CM to be effective.

Does Citrulline Enhance Aerobic Performance?

Earlier studies have suggested that citrulline supplements can improve aerobic performance by delaying fatigue by improving oxygen delivery and clearing metabolic waste like lactate during training. Some research has also indicated that citrulline can improve VO₂ max (the maximum amount of oxygen the body can use during exercise,) a key marker for aerobic capacity. In addition, citrulline users have reported feeling less fatigue or effort during exercise, possibly allowing them to train harder for longer.

However, current research does not support the claims of previous studies, according to a recent systematic review and meta-analysis.⁹

Citrulline supplementation did not significantly improve overall aerobic performance, oxygen uptake, or lactate levels when compared to a placebo.
Citrulline did not significantly change the rate of perceived exertion (RPE), meaning those who took the supplement didn’t feel like the exercise was easier. A few studies noted a slight increase in blood lactate levels, indicating higher exertion during exercise but no substantial performance gain.
Chronic supplementation (over 6–16 days) showed a slight tendency towards positive effects, though still not significant. Acute dosing (1-3 hours before exercise) had no beneficial impact.

In short, citrulline supplementation, both acute (short-term) and chronic (long-term), does not show clear, consistent, or significant benefits for improving aerobic performance, reducing perceived exertion, or enhancing oxygen use during exercise.

Does Citrulline Build Muscle?

While a few studies show that citrulline boosts muscle protein synthesis, this is primarily during low-protein diets, which are not optimal for building muscle in the first place.

Only one study has looked at muscle gain in healthy adults when using l-citrulline supplements compared to a placebo.¹⁰ It showed that citrulline augmented lean mass during a strength training program, especially when combined with glutathione (an antioxidant produced naturally in the body and also available as a supplement).

In the study, 75 trained men performed an 8-week resistance training program combined with either glutathione + L-citrulline, L-citrulline-malate, or a placebo.

The results showed that glutathione + L-citrulline supplementation led to a significant increase in lean mass after four weeks compared to the placebo. However, this difference was not maintained after eight weeks.

Citrulline is not a direct muscle-building compound like protein or certain anabolic agents. That being said, citrulline might allow you to do a few more reps during high-intensity strength training. By allowing you to train harder and for longer periods, citrulline may indirectly support muscle growth when combined with an effective strength training program and proper nutrition.

Does Citrulline Burn Fat?

Citrulline supplements are not primarily known as “fat burners,” but some recent studies suggest they might help with fat loss.

The first is an animal study.¹¹

In this study, citrulline supplementation reduced fat accumulation in the liver and improved metabolic health by increasing lipid oxidation and reducing fat production.

However, this research was conducted on rats. The findings might look promising, but further studies are required to confirm if the results apply to humans.

A more recent study examined how combining intense exercise with citrulline affects the body composition of older adults.¹²

When older, obese adults did high-intensity interval training (HIIT) with citrulline supplementation, the reseachers saw a more significant decrease in their body fat compared to a control group who did HIIT without citrulline.
Citrulline seemed to help trigger fat loss by influencing certain proteins and pathways in fat tissue. Specifically, it reduced the expression of a protein called CIDEA, which is involved in fat storage.

Despite this small study, current research does not support citrulline supplementation as a major factor for losing fat. It might have some small part to play when it comes to how exercise reduces body fat, but citrulline alone likely does not cause fat loss.

Does Citrulline Lower Blood Pressure?

According to a 2019 meta-analysis, L-citrulline supplementation shows a potential benefit for lowering blood pressure.¹³

It found a significant reduction in systolic blood pressure (SBP) with a mean difference of −4.10 mm Hg.
For diastolic blood pressure (DBP), a significant reduction, with a mean difference of −2.75 mm Hg, was observed, but only in studies using doses of 6 grams per day or more.

A major limitation of the research on the effects of citrulline on blood pressure is that most studies only examine healthy participants. Therefore, it is currently unknown if the results apply to those who would benefit the most: people with high blood pressure or other cardiovascular risk factors.

In addition, most studies are small, lasting only four weeks at most, and have few participants.

The researchers concluded that while it might be premature to recommend citrulline supplements as a means to prevent high blood pressure, eating a healthy diet with foods high in citrulline, like watermelon, could be a good idea.

Possible Effect on Erectile Dysfunction?

Since citrulline increases nitric oxide levels, it may also have positive effects on conditions like erectile dysfunction (ED). It helps the body produce nitric oxide (NO), which increases blood flow and could improve the strength of an erection. Unlike direct L-arginine supplements, which are broken down by the body to a significant degree before they can take effect, L-citrulline avoids this issue and is more efficiently converted to L-arginine in the kidneys, increasing plasma arginine concentrations.

There is some evidence that citrulline can help with erection hardness and might restore normal erectile function in men with ED.

A 2011 study examined the effects of L-citrulline on men with mild erectile dysfunction (ED).¹⁴ The researchers wanted to see if L-citrulline improves erection hardness.

In the study, 24 men, with an average age of 56.5 years, who had mild ED (erection hardness score of 3 of 4, meaning the penis is hard enough for penetration but not completely rigid) were tested in a single-blind study.

The participants took a placebo pill for one month and then L-citrulline (1.5 grams daily) for another month. The researchers tracked erection hardness, the number of sexual intercourses per month, patient satisfaction, and any side effects.
50% of the men reported improved erection hardness after taking L-citrulline, compared to only 8.3% who reported improvements with the placebo.
The average number of intercourses increased from 1.37 per month at the start to 2.3 per month after taking L-citrulline. All patients who saw improvements in erection hardness were very satisfied with the treatment, and no one reported any adverse effects.

The researchers concluded that L-citrulline is safe, well-tolerated, and can improve erection hardness in men with mild ED. Though not as effective as PDE-5 inhibitors like Viagra, L-citrulline could be a natural and less expensive alternative, especially for men who are uncomfortable with stronger medications or experience side effects.

Effects on Immunity and Oxidative Stress

Citrulline supplementation has several notable effects on the immune system and how the body manages oxidative stress.¹⁵

One is that it can reduce the number of certain immune cells, like leukocytes and neutrophils, which are linked to inflammation. Citrulline may also help protect blood vessels by producing nitric oxide, which can prevent immune cells from sticking to blood vessel walls and causing damage.
In addition, citrulline helps the body neutralize harmful molecules related to oxidative stress, like damaged proteins and lipids, which can harm cells. One study found that professional cyclists who took citrulline before a race experienced beneficial effects such as improved oxidative stress markers, from nitric oxide production, without any harmful effects.

However, the exact way citrulline improves immunity and manages oxidative stress is not entirely clear. While NO plays a role, other substances, like those produced from arginine and ornithine, and citrulline’s antioxidant properties may also contribute to these benefits.

Does Citrulline Affect Hormones?

Ctrulline may have a mild effect on anabolic hormones like growth hormone post-exercise but does not appear to significantly impact insulin or cortisol levels either at rest or post-exercise.¹⁶ ¹⁷

Most of its potential benefits are tied to improved performance and recovery, primarily through enhanced blood flow rather than direct hormonal modulation.

Safety of Citrulline

Citrulline is considered safe for oral use, even at high doses.¹⁸ It has no known toxic effects and has been safely used for long periods of time in medical settings, including in children.

Unlike similar amino acids like arginine and ornithine, which can cause digestive issues even at moderate doses, citrulline doesn’t seem to cause stomach problems like diarrhea or pain, even at doses up to 15 grams.

Several studies have confirmed the safety of citrulline. For example, children undergoing heart surgery experienced no adverse effects from citrulline supplementation, and similar results were found in other trials, including intravenous administration.

However, if you already take blood pressure medicines, adding citrulline might be contraindicated as it might cause blood pressure to go too low.

Recommended Dosages and Timing

The recommended dosage and timing of citrulline and citrulline malate supplementation are as follows, based on current research.⁵

Dosage: Most studies recommend an effective range of 6–8 grams of citrulline malate or pure L-citrulline. Higher doses, such as up to 15 grams, are well-tolerated, but benefits seem to plateau around 10 grams due to saturation effects.
Timing: Citrulline is typically taken 60 to 90 minutes before exercise. While this protocol is widely used, there is still uncertainty about optimal timing because plasma citrulline levels rapidly decline after reaching a peak approximately one hour after ingestion.

When using citrulline malate, the citrulline-to-malate ratio commonly used is 2:1 (two parts citrulline to one part malate). This ratio is most frequently studied and might provide a synergistic effect, potentially enhancing energy production and reducing fatigue. Malate may assist in the production of ATP and reduce the buildup of lactic acid during training.

There is limited research directly comparing different citrulline-to-malate ratios, but the 2:1 formulation is the most prevalent and appears to effectively balance the benefits of both components.

Using citrulline daily for at least a week seems to be more effective than taking a single dose pre-workout to enhance exercise performance.

In summary:

Recommended dosage:

8 grams of l-citrulline or citrulline malate for exercise performance. Larger doses (up to 15 grams) of citrulline may offer greater benefits but need more investigation.
6 grams or more daily for blood pressure reduction.
At least 1.5 grams per day for erection hardness, although anecdotal evidence suggests benefits from at least doubling that dose.

Timing:

1 hour before exercise

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