12 Evidence-Based Benefits of L-Citrulline

Like most, I am sure you are curious due to the many claims made regarding the life-altering benefits of L-citrulline.

As I too was curious about this funnily-named substance, I decided to do a little research to answer the many questions I had regarding the benefits of L-citrulline.


What is L-Citrulline?

L-citrulline is an amino acid made naturally by the body that has many positive health benefits.

Just a few of these benefits are support for heart health, improvement in strength and stamina, and relief from erectile dysfunction (1).

The word citrulline is a derivative of the Latin Citrullus, which is also the Latin word for watermelon.

This is due to the fruit’s high concentration of the amino acid (2).

As mentioned before, L-citrulline is manufactured naturally in the body, but extra needed amounts can be attained through both supplementation and dietary means.

Some foods that are especially high in L-citrulline are:

  • Watermelon
  • Dark Chocolate
  • Cucumbers
  • Almonds
  • Pumpkin

The body produces L-citrulline in the liver and the small intestines, and the amino acid is most often a byproduct of the precursor L-glutamine.

The majority of L-citrulline in the body is converted to L-arginine, which is then converted to nitric oxide, a gas that helps to dilate blood vessels.

Oddly, L-citrulline’s supplementation is more effective at producing L-arginine than supplementing with L-arginine itself.

The science behind this is that L-arginine is quickly removed from the body by the gut enzyme arginase (3).

Directly supplementing with L-arginine also can expose the taker to side effects such as diarrhea, vomiting, and nausea when taken at higher doses.

L-citrulline is both more efficient and more comfortable to supplement of the two amino acids.

However, the two substances taken in conjunction have proven to have synergistic benefits, and a greater effect on nitric oxide levels than either substance would on its own (4, 5).


How Does L-Citrulline Function in the Body?

L-citrulline, along with L-arginine and L-ornithine, is one of a trio of amino acids that are present in the urea cycle.

The urea cycle is responsible for converting toxic ammonia into urea and then expelling the substance from the body by the process of urination.

Once L-citrulline is ingested, the kidneys convert the substance to another of the urea cycle’s amino acids, L-arginine.

The kidneys then release the L-arginine into the bloodstream, which causes full-body availability of the amino acid (6, 7).

L-arginine is a precursor to the gas nitric oxide, and the gas is produced from L-arginine through a process called nitric oxide synthase.

NO plays a vital role in immune system support and healthy heart function.

Many of the positive benefits attributed to L-citrulline are due to the end product nitric oxide (8).

L-citrulline is also sometimes formed as a result of nitric oxide synthase, and during this process is formed from arginine.

This L-citrulline can then be recycled into arginine once more, in a process called the citrulline-NO cycle (9).


Health Benefits of L-Citrulline

There are many positive health benefits that can be achieved by L-citrulline supplementation.

These benefits have been well-researched, and are backed by a large number of clinical studies.


Boosts Muscle Endurance and Eliminates Muscle Soreness

A study conducted in France used 18 male subjects who, though complaining of fatigue, had not been diagnosed with any illness or disease.

The energy-boosting effects of citrulline had been previously observed, but the aerobic energy production of citrulline at the muscular level had yet to be determined.

All 18 men studied reported feeling less fatigue than before the study, and it was documented that the L-citrulline supplementation resulted in a rise in production of creatinine phosphate, an energy form present in muscles (10).

A second study, performed at the University of Cordoba in Cordoba, Spain, sought to measure the effects of a single dose of citrulline on the ability to perform flat barbell bench presses.

Men in the study that were given citrulline were able to perform more bench press repetitions and reported less muscle soreness in the periods after exercise (11).

I am pretty sure that the increase in muscle energy provided by citrulline is becoming clear to you, but here is one more study on this matter for you to consider.

The Healthcare Products Development Center in Japan studied the effects of cycling times using 22 trained male cyclists.

One group of cyclists was given 2.4 grams of citrulline, and the other a placebo for one week.

The group of men that were given the citrulline posted faster times for the 4-km cycle and experienced less muscle fatigue than the cyclists who were given the placebo (12).


Lowers Blood Pressure

The Sport and Health Sciences department at the University of Exeter’s St. Luke’s Campus in Exeter, United Kingdom provided proof regarding the ability of citrulline to lower blood pressure by supplementation of the amino acid.

In the study, a group of twelve men underwent a supplementation regimen of 6 grams of both citrulline and arginine for seven days.

The study concluded that L-citrulline caused a decrease in systolic blood pressure, and marked increases in levels of nitric oxide.

L-arginine was shown to play no role in the lowering of the systolic blood pressures of the male subjects (13).

A similar study, this time performed by researchers Paige Alsop and David Haughton, also used 12 healthy young men to measure the effects of citrulline supplementation on blood pressure.

Citrulline was shown to decrease both the diastolic as well as the systolic blood pressures of the 12 young men (14).


Helps Sufferers of Erectile Dysfunction

A single-blind study performed at the University of Foggia in Italy studied the effects of L-citrulline using 24 men past the age of 55 who were documented sufferers of mild erectile dysfunction.

The method of the study was simple, whereby one group of men was given 1.5 grams daily of L-citrulline, and another group of men was given a placebo for one month.

Fifty percent of the men given the L-citrulline reported normal erection strength and increased their frequency of intercourse (15).

If the numbers from that study failed to excite you, wait until you digest this one.

A recent Japanese study involving 15-week old rats divided the rodents into three groups.

There was a control group, a group of castrated rats, and a group of castrated rats that was given L-citrulline.

The conclusion drawn from the study was that L-citrulline supplementation improved the erectile response ability in rats that had been castrated (16).


Improves the Condition of Patients with Heart Failure

There have been multiple studies conducted that have proven without a doubt that L-citrulline can help to strengthen the hearts of individuals suffering from heart failure.

In one of these studies, conducted at a clinic in the country of Mexico, both L-citrulline and L-arginine were administered to subjects to evaluate the effects of the amino acids on heart failure patients determined to suffer from a condition known as preserved ejection fraction.

The study lasted for two months and conclusively demonstrated that both amino acids played a role in increasing the amount of blood flow through the right ventricle and decreasing the systolic pressure within the pulmonary artery (17).

A second Mexican study conducted at the same facility observed 35 outpatients being treated at the Heart Failure Clinic.

The experiment group was given three grams of L-citrulline orally daily, while the control group was given no supplementation.

The group that was given L-citrulline experienced significant improvements in the function of both ventricles, as well as endothelial function (18).


Increases Aerobic Workload Capacity for Exercise

Another great benefit that you will enjoy from an increased intake of L-citrulline is an overall increase in the amount of exercise that can be performed.

This is due to the aerobic performance-enhancing qualities of the amino acid.

A study at the Heart Failure Clinic in Salvador Zubiran, Mexico used 30 heart failure patients as subjects and demonstrated that patients given L-citrulline supplements were able to exercise longer on a treadmill than patients who were in the placebo group (19).

And as previously mentioned in a demonstration of L-citrulline’s ability to improve muscle endurance, subjects given the amino acid showed an increased capacity for exercise through bench pressing more repetitions or cycling faster on a 4-kilometer track.

This is also evidence of L-citrulline’s effect on aerobic capacity (20).


Ability to Increase Nitric Oxide Production in the Body

The main characteristic of L-citrulline that is the catalyst for all other positive contributions to health is the amino acid’s role in a chain of events that leads to a greater production of the gas nitric oxide in the body.

As mentioned before, this takes place when L-citrulline is converted to L-arginine, which is then converted to the nitric oxide needed to provide an assortment of positive health benefits.

A study conducted at the Healthcare Products Development Center attempted to measure the short-term effects of L-citrulline supplementation with regard to arterial elasticity.

In the study, a group of 15 men with an average age of 58 were selected based on criteria regarding arterial stiffness.

The men were then either treated with 5.6 grams of L-citrulline daily, or a placebo.

The treatments took place for seven days.

The L-citrulline group displayed a significant improvement in arterial stiffness over the placebo group, as well as greatly increased nitric oxide levels (21).

Another study was done on 10 children suffering from a mitochondrial disorder known as Melas Syndrome.

This condition is known to cause patients to suffer from an impairment in nitric oxide production, and the study sought to determine if L-arginine and L-citrulline supplementation would prove effective at correcting this defect (22).

The study was conducted by taking five children afflicted with Melas Syndrome and five children as a control group that were unaffected by the disease.

The study concluded that both L-arginine and L-citrulline significantly increased nitric oxide levels for children with Melas Syndrome.

The study also determined that the greatest benefits were derived from supplementing with L-citrulline.


Provides Immune System Support

You have probably come to the conclusion by now that L-citrulline is worth its weight in gold with regard to its beneficial health properties.

But if you are still on the fence, there is more to love about this amino acid.

A laboratory study in Spain was tasked with determining the effect on the immune system of L-citrulline supplemented orally.

The study observed 17 professional male cyclists assigned by a random method either to a supplement or to a control group.

Blood samples were collected from the cyclists immediately after races, and then again three hours later.

Supplemental citrulline was found to increase the plasma concentration for both citrulline and arginine in the group that was given the supplements (23).

It was also determined that L-citrulline supplementation directly benefitted a particular type of white blood cells, named neutrophils, in fighting infection when given orally before taking part in an exercise.

A second study demonstrating the immune-boosting potential of L-citrulline focused on the effect that arginine and citrulline had on the immune response to sepsis.


Remedies Disorders of the Urea Cycle

Urea cycle disorders are genetic conditions that cause an inability to detoxify properly the body of ammonia.

Patients who are afflicted with hyperammonemia often suffer serious health consequences, including the possibilities of neurological disorders or death.

L-citrulline has been used as a therapeutic option to address a variety of urea cycle disorders.

A recent report from Japan demonstrates the effectiveness of citrulline in treating these ailments (24).

The study was conducted via a survey of 43 sufferers of urea cycle disorders.

The survey took into account the patient’s background, the scope of L-citrulline supplementation, clinical data associated with the patient’s urea cycle disorder, and other relevant information.

The study concluded that L-citrulline supplementation was effective at reducing levels of ammonia, increasing intake of protein, and promoting weight gain in patients with urea cycle disorders.

The suggestion based on the study was that L-citrulline should be considered for use as a primary therapy for urea cycle disorders.


May Treat Sickle Cell Anemia

Sickle cell anemia is a genetic disorder of the red blood cells that can result in blood vessel blockage by abnormally-shaped red blood cells.

Sickle cell anemia is also often associated with decreased levels of nitric oxide in patients.

An increase in nitric oxide, a substance with the ability to dilate blood vessels, would benefit the patient by working to prevent the blockage of these blood vessels.

A study testing this theory was done by researchers in Greenville, North Carolina.

In the study, L-citrulline was given orally to sufferers of sickle cell disease twice daily.

The results of this study were both swift and dramatic.

Arginine levels in blood plasma rose significantly, and the patients experienced decreases in leukocyte and neutrophil counts to or near normal levels.

Continued L-citrulline supplementation in these subjects resulted in a continued decrease in negative symptoms (25).

Oral supplementation of L-citrulline is concluded to be a viable alternative for palliative care for patients with sickle cell disease.


May Increase Growth Hormone

Vigorous exercise for prolonged durations can result in the rapid breakdown of amino acids, resulting in a decreased availability of L-arginine.

L-citrulline supplementation is known to raise blood plasma concentrations of L-arginine, and increase the body’s ability to produce nitric oxide.

A study conducted by researchers in Spain intended to measure the impact of L-citrulline supplementation prior to intense exercise, with regard to the metabolism of amino acids in the blood plasma, as well as the specific metabolism of arginine and effects on hormone levels (26).

The study randomly assigned 17 volunteer male cyclists either to a supplement group or to a control group.

Participants took part in a 137 km cycling stage.

Blood samples were taken 15 minutes after the race’s finish, and then again three hours after the race.

It was found that most essential amino acids were decreased as a result of exercise, but the opposite proved true for non-essential amino acids.

Citrulline supplementation significantly increased blood plasma concentrations of citrulline, arginine, creatinine, nitrite, omithine, and urea.

Growth hormones were found to be increased in both groups after exercise, but a greater increase was realized by members of the supplement group.


Increases Blood Flow

Researchers at the Department of Kinesiology and Sports Management at Texas Tech University set out to find the answer for what effect short-term L-citrulline supplementation has on peripheral dilation and blood flow during exercise in adults of advanced age.

The main finding of the study was that L-citrulline provided an increase of 11% for femoral blood flow, and 14% for vascular conductance after exercising lower limbs (27).

This notable improvement in blood flow to the muscles is cause for optimism for the possibilities of increased exercise capacity for older adults.

Another study, this one completed in the UK, observed 10 young men with no known medical conditions and found that L-citrulline supplementation had a significant effect on blood flow (28).


Possible Risks and Side Effects

Documented side effects of L-citrulline supplementation are minimal.

There have been instances of subjects reporting mild discomfort caused by an upset stomach after taking L-citrulline.

Generally speaking, L-citrulline supplementation is a safe alternative for most, with no serious health risks associated.

It is suggested that women who are pregnant, as well as individuals taking medications for heart disease, sexual dysfunction, or high blood pressure, consult with their physician before supplementing with L-citrulline.


Dosing Suggestions

The recommended dosage for L-citrulline supplementation differs, depending upon the particular need being addressed.

  • Erectile Dysfunction – Individuals seeking to address erectile dysfunction concerns with L-citrulline supplementation will benefit from 1500 mg of L-citrulline daily.
  • Enhance Endurance – Fatigue reduction and increased capacity for exercise can be gained by supplementing with 2400 mg of L-citrulline daily.
  • Heart Failure – Clinic studies have been conclusive in demonstrating that taking 3000 mg of L-citrulline daily can address complications resulting from heart failure.
  • Blood Pressure – Individuals with a predisposition to hypertension can benefit from 3000 mg of daily L-citrulline intake.

L-citrulline supplementation can also be done in the form of citrulline malate.

Six to eight grams of daily citrulline malate intake has proven useful for increasing athletic performance, muscle endurance, and the capacity to tolerate aerobic exercise.


Do’s and Don’ts

The positive benefits to be gained by adding L-citrulline to a daily supplementation regimen has been proven clinically through a variety of studies.

It is of further benefit to the user that the positive effects of L-citrulline usage come with few to no side effects.

A variety of physical issues can be addressed via daily intake of L-citrulline, including, but not limited to:

  • Hypertension
  • Erectile Dysfunction
  • Minimized Exercise Capacity
  • Circulatory Problems
  • Heart Failure
  • Sickle Cell Disease
  • Disorders of the Urea Cycle
  • Low-Functioning Immune System

Dosage requirements for L-citrulline are associated with the user’s particular desired outcome, but all doses are generally considered safe.

A conversation with a medical professional may be in order before supplementing with L-citrulline if you are:

  • Pregnant or a nursing mother.
  • Taking prescription medications for hypertension.
  • Taking prescription medications for heart disease.
  • Taking medications or other supplements for erectile dysfunction.



What is L-citrulline?

I have concluded that this important amino acid has the capability to be many different things to different people.

But I am sure you will agree that L-citrulline’s benefits are so potent that increasing your intake of this amino acid is a good choice.

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


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