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Citrulline

L-Citrulline is an amino acid. It is efficiently turned into L-arginine in the kidneys after supplementation, which makes it a good choice for increasing nitric oxide synthesis in the body.

Our evidence-based analysis on citrulline features 107 unique references to scientific papers.

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Summary of Citrulline

Primary information, health benefits, side effects, usage, and other important details

What is Citrulline?

L-Citrulline is one of the three dietary amino acids in the urea cycle, alongside L-arginine and L-Ornithine. Taking L-Citrulline increases plasma levels of ornithine and arginine and improves the ammonia recycling process and nitric oxide metabolism. Consequently, it is used in areas where nitric oxide is relevant, namely athletic performance, and vascular health, and erectile dysfunction. There are very few foods that have notable amounts of citrulline, watermelon being a notable exception.

What are Citrulline's benefits?

In general, much research suggests a modest reduction in blood pressure and improvement in blood flow from chronic citrulline supplementation, particularly for those with hypertension and other cardiovascular problems. Limited research suggests an improvement in power output, a reduction in fatigue and improved endurance for both aerobic and anaerobic exercise. Many of the studies have used acute citrulline supplementation, and it's possible that there's an effect there, but benefits are more likely to be found from chronic supplementation. More research for erectile dysfunction but a small amount of research is supportive of a beneficial effect. There's more positive research for arginine, and citrulline increases arginine levels so it's plausible that it's also effective for this purpose.

What are Citrulline's side effects and drawbacks?

It's not known to have notable side-effects, though more research is needed to confirm its long-term safety when taken in high doses. Unlike L-arginine and L-ornithine, very high doses don't seem to result in gastrointestinal upset.

Is arginine or citrulline better?

A small amount of research suggests that taking citrulline will lead to higher and more consistent arginine levels than taking arginine. Citrulline is very readily converted to arginine as needed, and it is also better absorbed than arginine, which not only makes it a better source of arginine for the body but can mean a lower rate of gastrointestinal upset than arginine when taken in high doses.

What is citrulline malate?

Citrulline bound to malate, an organic salt of malic acid, an intermediate in the citric acid cycle. It is the most researched form of citrulline, and there is speculation about an independent role of malate in producing performance benefits, but there's insufficient research to compare citrulline malate to L-citrulline directly. Citrulline malate can be taken in the dose used in studies, but it's important to keep in mind that 1.76 g of citrulline malate is needed to about 1 g of citrulline.

?? Want a quick summary of citrulline's potential benefits?

We've analyzed over 100 studies to summarize the research on citrulline's potential health benefits.

How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

To supplement L-citrulline for circulatory health or to alleviate erectile dysfunction, take 2,000 mg of citrulline, three times a day with meals, for a total daily dose of 6,000 mg. L-citrulline does not need to be taken with meals, however.

To supplement for circulatory health with a citrulline malate supplement, take 1.76 g of citrulline malate for every 1 gram of citrulline you would normally take.

To supplement L-citrulline to enhance sports performance, take 6,000 – 8,000 mg of citrulline malate about an hour before exercise. On days that you don't exercise, it can be broken up into smaller doses.

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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Citrulline has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Minor Moderate See all 19 studies
A decrease in blood pressure is noted secondary to increasing plasma arginine (and thus increasing nitric oxide). It applies to both resting and active blood pressure, and to healthy and hypertensive participants in general, though the reduction will naturally be greater for those with hypertension.
grade-b Minor Very High See all 8 studies
There seems to be a distinction between acute and chronic supplementation; whereas acute citrulline supplementation doesn't seem to reliably improve performance, the studies that gave citrulline for a week prior to testing saw improvements. Additionally, a meta-analysis found a small but statistically significant increase for studies overall.
grade-b - Very High See all 6 studies
There do not appear to be any significant influences of supplemental citrulline on blood glucose concentrations in healthy participants. It is possible that there's some benefit of citrulline in diabetic people, but much more research is needed.
grade-b - Moderate See all 8 studies
No significant influence on heart rate seems likely, although some studies suggest a small reduction during and around the time of exercise, but this effect is inconsistent.
grade-b - High See all 4 studies
Most studies note that there is no significant change in insulin concentrations, although a lone study (not replicated) suggested that the exercise-induced increase in insulin was suppressed with citrulline. As this study also noted performance degradation, it may be a flaw
grade-c Notable Moderate See all 3 studies
The decrease in fatigue during exercise is thought to underlie most of the benefit seen with training capacity (work volume), although in men who self-report fatigue issues supplemental citrulline appears to help with that as well (independent of exercise)
grade-c Notable Very High See 2 studies
Nitric oxide derivatives (nitrate and urinary cGMP, since nitric oxide itself is hard to measure these biomarkers are indicative of nitric oxide production) appear to be reliably increased following oral consumption of citrulline supplementation
grade-c Notable Very High See all 4 studies
Citrulline can increase plasma arginine concentrations, and due to acting as a resevoir of arginine it is actually more effective overall at increasing plasma arginine than arginine itself (acute peaks are still observed to a higher level with arginine supplementation).
grade-c Notable - See study
The increase in work capacity seen with citrulline supplementation appears to be time dependent. While there are no inherent and immediate effect, the reduction of fatigue later in a weight lifting workout causes a relative increase that has at least one doubled reps conducted (on set 8 of exhaustive exercise)
grade-c Minor - See all 3 studies
Some improvement in cycling time trial performance has been found in a couple of studies, though the time to exhaustion in another wasn't improved. Much more research is needed to understand when citrulline might be effective.
grade-c Minor High See all 4 studies
Overall, there has been a reduction in arterial stiffness in most studies, particularly when in response to cold stress. More research is still needed to evaluate the effects on arteries of elderly participants with atherosclerosis.
grade-c Minor Very High See all 6 studies
An increase in blood flow is noted with citrulline supplementation in persons with impaired blood flow, and one study found an improvement in healthy participants, though much evidence is needed.
grade-c Minor - See 2 studies
A notable reduction was found in one study that used 2 g daily in NAFLD patients, but another didn't find an effect in middle-aged, healthy men. Much more research is needed.
grade-c Minor Very High See 2 studies
An increase in growth hormone has been noted with exercise, but not at rest. Practical significance of this information is unknown, since Arginine supplementation has unreliable effects itself
grade-c Minor - See study
Neutrophil oxidative burst post-workout appears to be enhanced when the exercise is preloaded with citrulline supplementation
grade-c Minor - See 2 studies
One study found a notable reduction from continuous use in type 2 diabetes whereas another didn't found one from acute supplementation prior to exercise.
grade-c Minor Very High See all 3 studies
Some studies have found a reduction when taking citrulline acutely prior to exercise, though this isn't entirely consistent and much more research is needed to confirm its effects.
grade-c Minor High See all 4 studies
Even though citrulline doesn't appear to reduce subjective fatigue, participants taking citrulline generally are able to perform more reps in muscle-fatiguing exercises.
grade-c Minor Moderate See 2 studies
Although acute usage does not appear to influence plasma glutamine, a week of high dose supplementation (0.18g/kg) has been noted to reduce glutamine concentrations slightly.
grade-c Minor Very High See 2 studies
An increase in plasma nitrate has been noted with citrulline supplementation, but not to the degree of supplemental nitrate itself
grade-c Minor - See all 4 studies
The effect seems to be fairly inconsistent, and it's not clear why, but reductions during physically demanding exercise have been noted.
grade-c Minor Very High See all 3 studies
An increase in urea is seen with citrulline supplementation (possibly due to increased serum ornithine sequestering ammonia)
grade-c - High See all 7 studies
It's possible that it can reduce the increase in lactate with exercise but the effect is hardly consistent.
grade-c - - See 2 studies
A slight increase in creatinine has been noted with one study but not another, practical relevance or cause unknown.
grade-c - - See study
No significant influence of citrulline on DNA damage
grade-c - - See study
No significant influence on HDL-C concentrations
grade-c - - See study
No demonstrated effects on IGF-1 concentrations following the usage of citrulline supplementation
grade-c - - See study
No significant influence on LDL-C concentrations in serum following citrulline supplementation
grade-c - - See study
No significant influence on lactate production seen with citrulline supplementation before exercise
grade-c - Very High See 2 studies
Studies haven't found a notable effect on AST, ALP, LDH, or ALT, but none have been conducted in participants with liver disease.
grade-c - High See all 4 studies
Most research hasn't found an effect in a variety of scenarios involving intense physical exercise. However, the one that did found a reduction in fatigue used it chronically over the course of a week, instead of acutely prior to exercise. It's unclear if this distinction matters and more research is needed, though it makes some sense. It should be noticed that this refers to subjective assessment of muscle fatigue, whereas muscular endurance refers to objective measures of the number of reps that can be performed.
grade-c - - See study
Currently no human evidence to support a practically significant increase in muscle protein synthesis at rest with citrulline supplementation
grade-c - - See study
No significant influence on total cholesterol concentrations
grade-d Notable - See study
One study in patients with systolic heart failure found a notable increase.
grade-d Notable - See study
A decrease was found in NAFLD, whereas the placebo group saw a notable worsening.
grade-d Minor - See study
Antioxidant capacity increased significantly in one study in type 2 diabetes.
grade-d Minor - See study
One low-quality study found a reduction in severity, but it wasn't statistically significant, and much more research is needed.
grade-d Minor - See study
The difference in one study had more to do with the placebo group seeing an increase due to exercise than citrulline seeing a reduction, but it can be interpreted as attenuation of the increase.
grade-d Minor - See study
Hardness of erections in persons with mild erectile dysfunction appears to be increased following supplementation of citrulline supplementation.
grade-d Minor - See study
There was an improvement in 6-minute walking distance for patients with hypertension and Eisenmenger Syndrome ion one study.
grade-d Minor - See study
Citrulline has been noted to increase physical exercise capacity in persons with heart failure.
grade-d Minor Moderate See 2 studies
An increase in muscle ATP production via aerobic means was noted in men given 6g citrulline daily, but this appeared to be attenuated with time. In another study, there didn't seem to be a notable difference.
grade-d
Minor
- See study
Improved for young but not old participants, and men but not women in one study. More research is needed.
grade-d Minor Very High See 2 studies
In persons with heart failure with normal ejection fractions, right ventricular ejection fraction during exercise appears to be increased relative to control.
grade-d Minor - See study
Handgrip strength was improved in female tennis players in one study.
grade-d - - See study
Actually cycling. One instance of a Wingate test didn't find a meaningful effect.
grade-d - - See study
No apparent effect on glutathione peroxidase or superoxide dismutase in one study in type 2 diabetes.
grade-d - - See study
No apparent effect of 6 g for 8 weeks.
grade-d - - See study
No apparent effect in one study.
grade-d - High See all 3 studies
Overall, studies haven't found a notable effect on cycling endurance, though more research in different contexts is needed.
grade-d - - See study
No apparent effect in one study.
grade-d - Moderate See 2 studies
Mixed evidence, more research is needed.
grade-d - - See study
No apparent effect in one study.
grade-d - - See study
No apparent effect in one study.
grade-d - - See study
No apparent effect in one study.
grade-d - - See study
No apparent effect on fibrosis in one study.
grade-d - - See study
No apparent effect on steatosis in one study.
grade-d - - See study
grade-d - - See study
grade-d - - See study
No apparent effect in one study.
grade-d - - See study
No apparent effect in one study.
grade-d - - See study
No apparent effect in one 8-week study.
grade-d - - See study
No apparent effect in one study.

Studies Excluded from Consideration

  • Confounded with the inclusion of L-arginine[1]

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Frequently Asked Questions and Articles on Citrulline

Combining citrulline with glutathione could increase your pump

Things to Note

Other Functions:

Primary Function:

Also Known As

L-Citrulline, Stimol (Brand Name), Watermelon extract

?? Want a quick summary of citrulline's potential benefits?

We've analyzed over 100 studies to summarize the research on citrulline's potential health benefits.

Click here to see all 107 references.