Does L-Citrulline Have Health Benefits?

Does L-Citrulline Have Health Benefits?

Does L-Citrulline Have Health Benefits?

L-citrulline is a naturally-occurring amino acid that has many purported health benefits. People use it to increase strength and stamina, improve erectile dysfunction, and support heart health. However, the majority of its uses are not supported by proper studies. Read on to learn whether L-citrulline has evidence-based benefits.


L-citrulline is a non-essential amino acid, meaning that it is made in the body and is not required through diet [1].

The name citrulline comes from the word citrullus, the Latin word for watermelon, as the fruit contains this amino acid (1.1- 4.7 mg/g) [2].

L-Citrulline is available as a supplement and can be found in a variety of foods.

Foods that contain L-citrulline include [3, 1]:

  • Watermelon (highest amount)
  • Squash
  • Melons
  • Cucumber
  • Pumpkin

Though l-citrulline is found in some foods, it’s mostly produced from l-arginine (by fermenting l-arginine with special microorganisms) or synthetically [4].

L-citrulline supplements have not been approved by the FDA for medical use and generally, lack solid clinical research. Regulations set manufacturing standards for supplements but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

In the body, L-citrulline is produced in the liver and intestines, either from L-arginine (10%) or L-glutamine (90%) [1].

How is it different from L-arginine?

Some people believe that L-citrulline supplements are more effective than L-arginine supplements at increasing blood arginine levels.

They say L-arginine supplements are not as efficiently absorbed as L-citrulline and are quickly removed from the body due to the activity of arginase in the gut, while L-citrulline is easily absorbed and converted to arginine. Limited evidence supports this claim [5].

Additionally, L-arginine causes nausea, vomiting, and diarrhea in doses above 9 g, whereas L-citrulline seems to be less ly to cause these adverse effects [6]. However, proper safety trials are lacking.

Because they use different transporters in the gut when they’re absorbed, scientists think L-citrulline can be combined with L-arginine to increase arginine and nitric oxide levels greater than either one alone. This theory has yet to be confirmed [7].

Mechanisms of Action

Some researchers suggest that L-citrulline plays an important role in muscle strength, heart health, the production of important enzymes, and increasing arginine levels [8].

L-citrulline is one of the three amino acids in the urea cycle (the other two being L-arginine and L-ornithine). The urea cycle converts a toxic compound called ammonia into urea, which is then eliminated from the body through urine.

After ingestion, L-citrulline is converted to L-arginine by the kidneys and is released into the bloodstream by the kidneys so that it is available to the whole body [9, 10].

L-arginine is a precursor to nitric oxide. Nitric oxide synthase produces nitric oxide from L-arginine. Nitric oxide plays a crucial role in the immune system and heart and blood vessel health. Many of the benefits of L-citrulline are due to L-arginine and nitric oxide [11].

L-Citrulline is also formed as a by-product in the production of nitric oxide from arginine. It can be recycled back to arginine in what is known as the citrulline-NO cycle [12].

Purported Benefits of L-Citrulline

Remember to speak with a doctor before taking l-citrulline supplements. L-citrulline should never be used as a replacement for approved medical therapies.

1) Certain Urea Cycle Disorders

Urea cycle disorders are genetic disorders that are usually diagnosed in children and can impair the elimination of ammonia from the body [13].

L-Citrulline supplements can help treat certain urea cycle disorders by removing ammonia from the bloodstream and preventing a build-up of it [1, 14].

2) Exercise Capacity & Athletic Performance

L-citrulline is possibly effective for improving exercise performance.

A randomized clinical trial on 30 heart failure patients showed that citrulline may increase exercise capacity. Those who were given l-citrulline were able to exercise on a treadmill for longer [15].

As previously mentioned, healthy men who were given L-citrulline also saw an increase in exercise capacity, either by being able to do more bench presses or cycle faster [16, 17].

Additional research is needed.

3) Fatigue & Muscle Soreness Post-Exercise

A study of 18 men with fatigue found that L-citrulline reduced fatigue and increased ATP levels. Every man reported a reduction in fatigue after exercise. L-Citrulline also increased the production of creatine phosphate, which is a form of energy reserves in the muscles [18].

Another study of 41 men showed that citrulline malate reduced fatigue. Those receiving citrulline were able to do more reps per set of bench presses and experienced less soreness after exercise [16].

A study on 22 men found that L-citrulline increased cycling speed and reduced muscle fatigue compared to placebo [17].

Additional, large-scale clinical studies are needed to confirm this alleged benefit.

4) Heart Failure

L-citrulline is possibly effective for people with heart failure. Supplementing ly helps as an add-on strategy in people with heart failure taking standard medications.

A study of 30 patients with heart failure found that l-citrulline increased the volume of blood pumped the right ventricle of the heart and lowered blood pressure in the pulmonary artery [15, 19].

A study of 35 patients revealed that L-citrulline improved the function of both the right and left ventricles as well as endothelial function [20].

However, the safety and efficacy of l-citrulline in heart failure patients should be investigated further in large-scale studies.

Insufficient Evidence for:

The following purported benefits are only supported by limited, low-quality clinical studies.

There is insufficient evidence to support the use of l-citrulline or any of the below-listed uses.

5) Erectile Dysfunction

A single-blind study of 24 men over the age of 55 showed that L-citrulline improves erectile dysfunction (ED) and increases the hardness of erections. Some men reported having more sex after treatment and being more satisfied [21].

However, we can’t draw any conclusions from this small study, the findings of which have not been replicated. Further research should be encouraged.

L-citrulline supplements improved erectile dysfunction and reduced dysfunction caused by low blood pressure in rats. Scientists think this is ly due to an increase in nitric oxide [22, 23].

6) Increasing Nitric Oxide & Blood Flow

A study on 15 healthy men showed that those who received L-citrulline supplements had increased nitric oxide levels [24].

A study of 10 children with a mitochondrial disorder found that L-citrulline supplements effectively increased nitric oxide levels due to an increase in arginine [25].

More clinical trials are needed.

Furthermore, clinical research is lacking to determine the effects of l-citrulline on blood flow.

A combination of L-citrulline and L-arginine supplements increased blood flow in the ears of rabbits [26].

A study of 10 healthy young men found that nitric oxide plays an important role in regulating blood flow [26]. Another study found that L-citrulline effectively increases nitric oxide [24, 25]. This suggests that L-citrulline may increase blood flow, though no human studies have been carried out.

7) Reducing Blood Pressure

Evidence does not back up the purported benefits of l-citrulline on blood pressure, though early studies are promising.

A study on 12 healthy young men showed that L-citrulline decreased systolic blood pressure and increased nitric oxide levels. Nitric oxide causes blood vessels to dilate, which lowers blood pressure [27].

Another study of 12 healthy young men found that L-citrulline decreases both systolic and diastolic blood pressure [28].

8) Effects on Growth Hormone

A study on 17 cyclists revealed that L-citrulline increased growth hormone levels after exercise, but not at rest. They hypothesized that this might’ve been due to an increase in arginine levels. Arginine blocks the release of growth hormone inhibiting hormone. Much more research is needed [29].

9) Immune Defense

A study on 17 male cyclists found that L-citrulline supplementation before exercise may boost immunity. Neutrophils (a type of white blood cell) of the cyclists supplemented with L-citrulline showed improved ability to fight infection. Additional research is needed, as we can’t infer anything from a single study [30].

10) Sickle Cell Anemia

A study of 5 African-American patients with sickle cell anemia showed that L-citrulline supplementation may be a useful complementary strategy for the disease. The patients treated with L-citrulline had reduced symptoms of the disease along with a decrease in white blood cells to normal counts [31].

The use of l-citrulline for sickle-cell anemia remains unproven until additional clinical trials are conducted.

L-Citrulline Side Effects & Precautions

The most common side effect is stomach upset [20, 16].

The following side effects have also been reported [32]:

  • Gastrointestinal intolerance
  • Heartburn
  • Changes in urinary frequency
  • Cough
  • Swelling

This list is not exhaustive. Limited safety data are available, so additional adverse effects cannot be ruled out [14].

Drug Interactions

Although there is no clinical evidence, L-citrulline supplementation may interact with drugs used to treat the following conditions: [1]

  • High blood pressure
  • Heart disease
  • Erectile dysfunction


L-citrulline dosage in clinical studies differed depending on what it was being used for.

For erectile dysfunction, 1,500 mg/day was used [21].

To reduce fatigue and increase workout capacity, 2,400 mg/day was given [17].

Heart failure patients received a dosage of 3,000 mg/day [15].

To reduce blood pressure, 3,000 mg/day was used [28].

L-citrulline can also be supplemented in the form of citrulline malate. Doses of 6 to 8 g of citrulline malate have been used to increase athletic performance and workout capacity [33, 34].

User Experiences

Many people claim that L-citrulline supplements are effective at increasing energy levels and exercise capacity when taken pre-workout.

Some people also report that L-citrulline is helpful for heart and overall health.

While most people were happy with the supplement, others reported that it did not work for them or that it caused them to feel sick.

The opinions expressed in this section are solely those of the users who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.

Do not consider user experiences as medical advice.

Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked.

We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.


The Health Benefits of Citrulline

Does L-Citrulline Have Health Benefits?

Citrulline is a natural supplement that is considered a non-essential amino acid. This means that the body can make its own citrulline; it can also be found in some foods (such as watermelon).

Citrulline is synthesized (made) in the liver and intestine; its function is to detoxify ammonia and act as a vasodilator (dilating the blood vessels). Citrulline is also said to have an antioxidant effect.

There are two forms of citrulline, available as a supplement; these include L-citrulline and citrulline malate. The primary difference between the two types of citrulline is that L-citrulline is simply citrulline without any other substance, and citrulline malate is comprised of L-citrulline, plus DL-malate (a compound that may be instrumental in converting food to energy.)

Citrulline (L-citrulline) is found under several other names, including:

  • 2-amino-5-(carbamoylamino) pentanoic acid
  • Citrulline malate
  • L-citrulina
  • L-citrulline malate
  •  Malate de citrulline

Although there is very little scientific research evidence to back many of the claims of L-citrulline health benefits, the natural supplement is said to have several health promoting properties, and is used for health conditions, including:

A 2010 randomized double-blind study (the gold standard of research studies) involving 41 men, discovered that a single dose of citrulline malate (CM) resulted in a significant increase in the number of barbell bench presses (accounting for 52.

92% more repetitions) and a 40% decrease in muscle soreness after exercise.

“We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve post exercise muscle soreness,” wrote the study authors.

Another study, published in 2017, looking at older individuals found citrulline modestly increased muscle blood flow during submaximal exercise in men but not women. The same study found that the diastolic blood pressure of the treated group was lowered in men but not women.

Cardiovascular (Heart and Blood Vessel) Health
Studies have shown that short-term L-citrullline supplementation can lower blood pressure in adults with hypertension (high blood pressure) and those with pre-hypertension.

These studies suggest that pharmaceutical/nutraceutical grade L-citrulline was instrumental in promoting heart health.

 “The safety and efficacy of long-term l-citrulline supplementation therefore requires further investigation,” concluded the study authors.

A paper published in 2019 reviewed 8 trials looking at adults. Their analysis of the data suggested citrulline can lower systolic blood pressure (by 4 mmHg).

A significant decrease in diastolic blood pressure was seen only at higher doses.

The authors felt it was too soon to recommend citulline supplements but that a diet rich in citrulline containing foods might contribute to the prevention of hypertension.

It’s important to note that there are several other (less potent) grades of supplements of which may be less effective (such as medical grade, nutritional grade, and cosmetic grade). Pharmaceutical grade must be more than 99% pure (from natural sources) and must contain no dyes, filler, binder or unknown substances.

L-citrulline is said to boost L-arginine, which in turn helps to elevate nitrogen oxide (NO) synthesis. NO promotes the relaxation of blood vessels, resulting in oxygen-rich blood circulating through the arteries. Therefore, L-arginine is said to promote heart health, but it is also important in erectile function (because of its blood flow promotion properties).

In a study of 24 participants from the age of 56 to 66, the use of L-citrulline was found to improve the erection score from 3 (mild erectile dysfunction) to 4 (normal erectile function) in 50% of the men who took it, as compared to improvement in 8.3% of the men who took a placebo.

The study authors concluded, “Although less effective than phosphodiesterase type-5 enzyme inhibitors [such as Viagra], at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychological fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.”

Studies have shown that some symptoms of sickle cell disease may be alleviated by taking a twice daily dose of L-citrulline by mouth. Not only was blood health improved with the administration of citrulline, study subjects also realized an improvement in overall well-being.

A double-blind clinical research study involving study participants with sickle cell anemia (SCA) discovered a link between an increased level of NO and a decrease in the frequency that the study subjects experienced pain.

L-citrulline is thought to promote an increase in the level of NO in the body, as well as promoting L-arginine levels.

 This study found that L-arginine supplementation may serve to potentiate the treatment of sickle cell anemia, but the study authors explained that more research is needed to evaluate the long-term safety and efficacy of these natural supplements.

In the body, L-citrulline is transformed into a different amino acid, called L-arginine, which is converted into a chemical called nitric oxide.

It is thought that L-citrulline may help to supply the body with the raw material it requires to make specific proteins.

L-citrulline may also act as a vasodilator (a substance that widens the veins and arteries to help improve blood flow while lowering blood pressure).

Citrulline has been used as an oral (by mouth) supplement) for many years, without reports of serious safety concerns. Although side effects of citrulline are uncommon, there have been some reports of mild symptoms such as nausea, indigestion, and diarrhea.

A contraindication is a treatment, medication, or procedure (such as surgery) that is not recommended because of a high potential of causing harm to the patient.

This means that in specific conditions (such as pregnancy) a medication, supplement, or procedure should not be given/performed.

It may also indicate that two specific medications (including prescription drugs, over the counter medications and natural supplements) should not be given together. Contraindications for L-citrulline include:

  • Pregnancy (there is not enough clinical research data to prove the safety of citrulline during pregnancy).
  • Breastfeeding (there is not enough clinical research data to prove the safety of citrulline during breastfeeding).

Those who are taking certain prescription drugs should not take citrulline, these include:

  • Phosphodieterase-5 inhibitors (medication for erectile dysfunction such as Viagra and Levitra) because both L-citrulline and phosphodieterase-5 inhibitors can lower blood pressure and the combination of these two medications together can cause hypotension (low blood pressure)
  • Nitrates (drugs that increase the blood flow to the heart): Taking nitrate medications (often used to treat angina) along with citrulline may result in an increase in blood flow to the heart that could cause side effects such as headaches, flushing, dizziness, fainting, low blood pressure (hypotension), or irregular heart rhythms (arrhythmia). Nitrate drugs include Dilatrate-SR and Isordil (isosorbide dinitrate), ISMO (isosorbide mononitrate), and Nitro-Dur, Nitrolingual or Nitrostat (nitrogylcerin).
  • Antihypertensive drugs (high blood pressure medications) such as Norvasc or Lotrel (amlodipine), Cardizem CD, Cardizem SR, Dilacor XR, or Tiazac (diltiazem), Calan SR ( verapamil), HydroDIURIL (hydrochlorothiazide), Lasix (furosemide), and more.

Other prescription medications could interact with citrulline and it could have a negative impact on certain clinical states (such as those with associated hypotension), hence its possible use should be discussed with a physician.

The FDA notes that limited safety data is available so safety issues cannot be ruled out.

L-citrulline is commonly available in a powder form that can be mixed with liquid or added to nutritional shakes.

For exercise performance enhancement, 2 to 5 grams of L-citrulline per day is an average dose. Studies have shown that doses of 3 to 6 grams per day of L-citrulline and 8 grams of citrulline malate can be taken with no side effects.

In fact, one study, conducted in France, discovered that taking up to 15 grams of citrulline was safe and well-tolerated by the study participants.

No side effects were reported, even when supplement doses of up to 20 grams of citrulline malate were taken.

Natural supplements (such as citrulline) are not regulated by the Food and Drug Administration (FDA) or any other governmental agency, prescription and over-the-counter drugs.

What this indicates is that the burden to ensure a person is buying a safe, pure and effective product, is on the consumer.

Simply reading the label may not provide enough information to make a well-informed buying decision on products such as citrulline.

It’s important to purchase a product that is organic, and one that has been certified by a third-party agency, such as the U.S. Pharmacopeia, NSF International, or These organizations evaluate and report on a product’s level of safety, purity, and potency.

How can I get citrulline in my daily diet?

Some of the best sources of citrulline from food include:

  • Watermelon
  • Bitter gourd
  • Squash
  • Nuts
  • Chickpeas
  • Pumpkin
  • Cucumbers
  • Gourds

Which type of melon is known to have the very highest level of citrulline?

Studies have been done to evaluate various types of melon to discover which variations offer the highest level of citrulline.

According to a study published by the journal, Journal of Horticulturae, “Watermelon is the most significant, natural plant source of L-citrulline, a non-proteinaceous amino acid that benefits cardiovascular health and increases vasodilation in many tissues of the body.”

Watermelon is a member of the Cucurbitaceae, which includes squash, melon, pumpkin, and cucumber.

The specific types of melon that Journal of Horticulturae study found highest in citrulline include:

  • Crimson Sweet watermelon
  • Dixielee watermelon
  • Casaba-type melon
  • Mouse melon
  • Horned melon rind
  • Bitter gourd


Top 6 Health Benefits of L-Citrulline

Does L-Citrulline Have Health Benefits?

L-citrulline is a non-essential amino acid, meaning that it is made in the body. It is produced in the liver and intestines, either from L-arginine or L-glutamine.

When deciding between L-citrulline supplements and L-arginine supplements, it is better to choose L-citrulline because it is more effective at increasing blood arginine levels.

This is because L-arginine supplements are not as efficiently absorbed as L-citrulline and are quickly removed from the body due to the activity of arginase in the gut.

L-citrulline is one of the three amino acids in the urea cycle. This is a process that converts a toxic compound called ammonia into urea, which is then eliminated from the body through urine.

These are the top 6 benefits of using a supplement that contains L-Citrulline:

1. L-citrulline can increase exercise capacity

It has been shown in several research studies that healthy adults who started taking L-citrulline saw an increase in exercise capacity. This is due to its ability to utilize your oxygen better which boosts your workout and endurance ability.

2. It increases blood flow

Nitric oxide plays an important role in regulating blood flow. Since higher levels of L-Citrulline have been shown to increase Nitric Oxide levels, we see a positive correlation between L-Citrulline and the increase of blood flow throughout the body.

3. L-Citrulline decreases blood pressure

We live in a time of information overload and a constant state of “being busy” which many people perceive as “stress”. When we get in these states of stress, we breathe shallow, which results in our pressure going up and our bodies getting tense. Over time, this becomes our new normal and we live with our blood pressure consistently sky-high.

Many studies have shown that L-citrulline helps decrease high blood pressure and increase nitric oxide levels. Nitric oxide causes blood vessels to dilate, which lowers blood pressure. In turn, the blood pressure will decrease. This is especially important because people who appear healthy and fit on the outside are often experiencing higher blood pressures.  

4. Improved cardiac function and erectile dysfunction

There have been direct links that show L-citrulline improves the function of both the right and left ventricles as well as endothelial function. We also see an improvement in erectile dysfunction due to the increase in blood and oxygen utilization.

5. Enhanced cognition & brain performance

The most common killer of cells is a lack of oxygen in our bodies. As previously mentioned, L-Citrulline helps utilize and maximize oxygen and blood flow throughout our bodies. When we are utilizing more oxygen, our cognitive function goes up and our brains perform at a higher level.

6. Boosts immunity

L-citrulline supplementation has been linked to the ability to fight infection by boosting our immune system and allowing our bodies to help fight foreign invaders naturally.

Interested in trying this health booster? Order our STAMINA product, formulated by Balance Docs, with the main ingredient being L-citrulline. This product will help your muscle strength, heart health, production of important enzymes, and increase arginine levels. Use stamina to increase sexual stamina and blood flow for better sexual performance, function and desire!

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L-Citrulline – Dietary Supplement, Side Effects & Interactions

Does L-Citrulline Have Health Benefits?

Amino acids are sometimes called “the building blocks of life.” The ones you acquire in your diet are called “essential amino acids” — you need to ingest them from other sources to live. Others, called “nonessential amino acids” because they are not essential to the human diet to survive, are created by your body.

One of these nonessential amino acids is L-citrulline. Its name comes from “citrullus,” the Latin word for watermelon, from which it was first isolated.

The kidneys break L-citrulline apart into another amino acid called L-arginine and the chemical compound nitric oxide (NO). Nitric oxide improves blood flow by relaxing arteries.

L-citrulline is produced in both over-the-counter (OTC) versions and as a pharmaceutical-grade medical ingredient.

OTC versions are popular with athletes attempting to gain an edge in endurance and strength. Studies have found that nitric oxide may improve sports performance, possibly through its effects on blood flow, muscles and metabolic actions.

Fact The U.S. Food and Drug Administration (FDA) does not regulate L-citrulline as a drug.

Pharmaceutical grade versions of this amino acid also play critical medical roles.

The U.S.

Food and Drug Administration (FDA) does not regulate L-citrulline as a drug, but it is considered a “medical food,” which the FDA defines as “a food which is formulated to be consumed or administered enterally [through the digestive tract] under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, recognized scientific principles, are established by medical evaluation.”

While the FDA does not consider L-citrulline a drug in itself, the agency lists pharmaceutical grade versions of it as a “bulk drug substance” or “active pharmaceutical ingredient” (API). Pharmaceutical grade L-citrulline can be manufactured as a powder; pharmacies may compound L-citrulline into tablets, capsules or liquids.

L-citrulline is used to treat a group of genetic disorders called inborn errors of metabolism (IEM). Left untreated, IEMs can result in developmental disabilities, brain damage and death.

One of these conditions affects the urea cycle – the body’s process of removing excess ammonia from the bloodstream. The National Urea Cycle Disorders Foundation estimates that up to 20 percent of sudden infant-death syndrome (SIDS) cases may be due to an undiagnosed IEM such as a urea cycle disorder (UCD).

UCD is rare. One 2013 study by Summar and colleagues predicted one disorder for every 35,000 births, or about 113 new patients each year.

People with a UCD have a genetic mutation. It prevents their bodies from making enough key enzymes for the cycle to work properly. These enzymes in a healthy person create chemical reactions that extract nitrogen from the blood and convert it into urea, a chemical compound that is then expelled from the body through urine.

In people with a UCD, nitrogen accumulates as ammonia in the blood stream. If it reaches the brain, it can lead to brain damage, coma and death.

There are six enzymes required for the urea cycle to function properly. A deficiency of any one of these can result in a specific disorder.

Carbamoyl phosphate synthetase I (CPS1) deficiencyMost severe UCD. Complete CPS1 in a newborn can rapidly advance to dangerously high levels of ammonia in the blood. Lifetime chronic risk of repeat high levels of ammonia if the newborn recoversN-acetyl glutamate synthetase (NAGS) deficiencyMimics CPS1 deficiencyOrnithine transcarbamylase (OTC) deficiencyIn males, OTC can be as severe as CPS1. While not as severe in females, about 15 percent of females with OTC deficiency develop dangerously high ammonia levels in blood during their lifetimes, often requiring chronic medical managementCitrullinemia type I (ASS1) deficiencySlightly easier to treat than other UCDs, but can still be severeArgininosuccinic aciduria (ASL) deficiencyCan result in rapid onset of dangerously high ammonia levels in the blood of newborns. May result in coma or death. Even in those who do not experience coma, may suffer significant developmental disabilitiesArginase (ARG) deficiency (also called hyperargininemia) Rapid onset of elevated ammonia levels in the blood are not typical but people with ARG deficiency may experience other severe symptoms including progressive spasticity, tremor, ataxia (the loss of full control of bodily movements), and choreoathetosis (involuntary movements including migrating contractions, twisting, and writhing)

While the disorders are most notable in children, they can also occur in adults who were born with a mild version of a mutation. Their condition may go unnoticed until their metabolic system comes under heavy stress from things viruses, excessive exercise or high protein intake.

UCDs are treated through diet, drug treatment, and in some cases, liver transplant. A transplant is the only cure for the disorder.

Short of a transplant, the condition is usually managed through diet and drug treatment.

The prescription drugs sodium phenylbutyrate, sodium phenylacetate, and sodium benzoate – sometimes called “ammonia scavengers” – may be used to help remove excess ammonia.

But any drug treatment regimen also requires patients to take an amino acid – either L-citrulline or L-arginine depending on the particular condition – for the drug to work properly.

Both L-citrulline and L-arginine accelerate urea cycle enzymes, promoting proper ammonia removal.

Because the body converts L-citrulline into nitric oxide (NO), it may benefit blood flow or other bodily functions in patients with certain medical conditions. Medical professionals may sometimes recommend it to help treat some diseases and disorders. However, there is limited information on the use of L-citrulline as an over-the-counter agent for many disorders.

L-citrulline May Be Assigned ForPotential Benefit
Erectile dysfunctionBeneficial effect on blood vessels
Alzheimer’s diseaseImproved effects of NO on the brain
DementiaImproved effects of NO on the brain
High blood pressureBeneficial effect on blood vessels
Cardiovascular diseaseBeneficial effect on blood vessels
Sickle cell disease – a group of disorders that affects red blood cells’ ability to deliver oxygen to cells in the bodyAdded NO may have a beneficial effect on patients

Since L-citrulline occurs naturally in the body, it is believed to be a safe supplement. There is not enough information available to determine for sure whether over-the-counter L-citrulline is safe to take. However, since there has been little research on how it might affect pregnant or nursing women, medical professionals recommend they not ingest L-citrulline supplements.

Fact There has been little research on how L-Citrulline might affect pregnant or nursing women – medical professionals recommend they not ingest it.

Because it affects some of the same bodily functions as drugs for high blood pressure, cardiovascular disease, and erectile dysfunction, patients should talk to their doctor if they are on any of those drugs before taking any prescription or over-the-counter L-citrulline product.

Studies of L-citrulline’s medicinal benefits beyond UCDs have been limited and inconclusive, but health care professionals may sometimes assign it for certain medical conditions.

A 2001 study of five patients with sickle cell disease found twice daily doses of L-citrulline, with amounts determined by patient weight, “resulted in dramatic improvements in symptoms of well-being” as well as blood health.

Fact Patients with sickle cell disease found twice daily doses of L-citrulline found improvements in symptoms of well-being as well as blood health.

In a 2010 study, patients who had suffered heart failure were given 3 grams of L-citrulline per day for two months. They were then placed on a treadmill for a stress test. Researchers found their blood pressure had “decreased significantly” while improving the function of the right ventricle in their hearts.

Another 2010 study found short-term L-citrulline supplementation may improve stiffness of arteries. Researchers found stiffness was “significantly reduced” compared to the placebo group, but noted no difference in blood pressure changes between the two groups.

A 2011 study compared L-citrulline to phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED).

PDE5 inhibitors include Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil).

While L-citrulline did not perform as well, researchers concluded that L-citrulline supplementation “proved to be safe and psychologically well accepted” by patients with erectile dysfunction.

“Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychological fear of [PDE5] inhibitors, deserves further research,” the researchers wrote.

Over the counter (OTC) versions of L-citrulline have been marketed as enhancing aerobic exercise as well as building, feeding and repairing muscle fibers. L-citrulline may help with blood flow, help muscles work better, and increase the body’s ability to use oxygen during exercise. But most studies of L-citrulline in this area have been made up of small groups and have been inconclusive.

A 2015 study gave 22 trained male cyclists 2.4 grams of either oral L-citrulline or a placebo once a day for eight days. On the eighth day, the men took their dose one hour before taking part in a 4 km (2.48 miles) time trial. Those taking L-citrulline had a finish time roughly 1.5 percent faster than those taking the placebo.

22 trained male cyclists took L-citrulline or a placebo. Studies showed those taking L-citrulline had a finish time roughly 1.5% faster than those taking the placebo

A 2016 study looked at using L-citrulline and L-arginine in alleviating exercise-induced fatigue. Researchers put 12 male taekwondo athletes through the equivalent of three martial arts matches.

Each match consisted of three, two-minute rounds.

At the end of the second match, some athletes were given a mixture of the two amino acids while others were given a placebo before continuing into the third match.

Researchers reported those given the L-citrulline and L-arginine performed “significantly better” than those given a placebo.

But other studies have shown L-citrulline may have a negative effect on performance or no effect at all. A 2006 study suggested runners on a treadmill actually became exhausted much sooner if given L-citrulline.


L-citrulline: Uses and Risks

Does L-Citrulline Have Health Benefits?

L-citrulline is a substance called a non-essential amino acid. Your kidneys change L-citrulline into another amino acid called L-arginine and a chemical called nitric oxide.

These compounds are important to your heart and blood vessel health. They may also boost your immune system.

L-citrulline boosts nitric oxide production in the body. Nitric oxide helps your arteries relax and work better, which improves blood flow throughout your body. This may be helpful for treating or preventing some diseases.

Ther is some evidence to suggest the supplement could possibly help lower blood pressure in people with prehypertension. This is an early warning sign for high blood pressure. It means you have a slightly raised blood pressure reading of 120/80 to 139/89. Prehypertension raises your risk for high blood pressure and heart disease.

L-citrulline supplements may ease symptoms of mild-to-moderate erectile dysfunction (ED). Scientists say L-citrulline does not work as well as ED drugs such as Viagra. However, it appears to be a safe option.

Animal studies suggest L-citrulline might also help people with blood vessel problems such as slow wound healing due to diabetes.

Other animal research says L-citrulline might improve muscle protein levels and prevent malnourishment in the elderly.

The animal research also suggests L-citrulline may help treat intestinal problems, including:

  • Short bowel syndrome
  • Celiac disease
  • Radiation-caused small bowel damage

Certain genetic disorders and health conditions such as liver disease may be helped by L-citrulline supplements.

Early human studies done also hint that L-citrulline may be helpful for Parkinson's disease and certain dementias.

Some people also take L-citrulline to build muscles and improve athletic performance. But research shows it does not help well-trained athletes perform or exercise better.

The supplement usually comes in powder form.

The suggested dosage for L-citrulline depends on what disease you are trying to treat or prevent, but is sometimes used up to 9 grams daily, divided throughout the day.

However, optimal doses of L-citrulline have not been set for any condition. Quality and active ingredients in supplements may vary widely. This makes it hard to set a standard dose.

Yes, watermelon contains L-citrulline.

There are no reported side effects of L-citrulline.

However, the supplement may affect the way certain drugs work in your body. Do not take this supplement if you are taking:

  • Nitrates for heart disease
  • ED drugs such as Cialis, Levitra, or Viagra

Combining L-citrulline with those drugs may cause a dangerous drop in blood pressure.

You should also be careful when taking L-citrulline if you take any type of blood pressure medicine.

Do not use L-citrulline if you are pregnant or breastfeeding.

Always tell your doctor about any supplements you are taking. That way, your doctor can check on any potential side effects or interactions with any medications.

The U.S. Food and Drug Administration (FDA) does regulate dietary supplements; however, it treats them foods rather than medications.


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National Medicines Comprehensive Medicines web site. “L-Citrulline Monograph.”

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