Evidence Based
9

Does L-Citrulline Have Health Benefits?

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

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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.

What is L-Citrulline?

Overview

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 likely 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

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

There are insufficient data to support the use of l-citrulline for any of the below listed uses, with the exception of some urea cycle disorders.

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) Helps Treat Urea Cycle Disorders

Urea cycle disorders are genetic disorders that 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) Fatigue and Muscle Soreness

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 [15].

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.

3) Exercise Capacity

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 [18].

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.

4) Heart Function

L-citrulline is possibly effective for people with heart failure. Supplementing likely 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 out of the right ventricle of the heart and lowered blood pressure in the pulmonary artery [18, 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.

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 likely due to an increase in nitric oxide [22, 23].

6) Increases Nitric Oxide

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.

7) Effects on Blood Flow

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.

8) 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].

9) 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].

10) Immunity

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].

11) 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.

Side Effects & Precautions

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

However, limited safety data is available, so safety issues 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

Supplementation

Dosage

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 [18].

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 [32, 33].

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.

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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