L-citrulline is a naturally occurring amino acid that has many health benefits, including increased strength and stamina, improvement in erectile dysfunction, and improved heart health. Read on to learn about the many health benefits of L-citrulline.

What is L-Citrulline?

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 large amounts of the amino acid (1.1- 4.7 mg/g) [2].

L-Citrulline can be taken 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

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

L-citrulline supplements are more effective than L-arginine supplements 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 easily absorbed and converted to arginine [4].

Additionally, L-arginine causes nausea, vomiting, and diarrhea in doses above 9 g, whereas L-citrulline does not [5]. This makes L-citrulline a better choice for increasing blood arginine levels.

Because they use different transporters in the gut when they’re absorbed, L-citrulline can be combined with L-arginine to increase arginine and nitric oxide levels greater than either one alone [6].

L-citrulline plays an important role in muscle strength, heart health, the production of important enzymes, and increasing arginine levels.

Mechanisms of Action

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 [7, 8].

L-arginine, 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 [9].

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 [10].

Benefits of L-Citrulline

1) Decreases 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 [11].

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 [12].

A study on 22 men found that L-citrulline increased cycling speed and reduced muscle fatigue compared to placebo [13].

2) May Increase Exercise Capacity

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 [14].

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 [12, 13].

3) Reduces 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 [15].

L-citrulline supplements improved erectile dysfunction and reduced dysfunction caused by low blood pressure in rats. This is likely due to an increase in nitric oxide [16, 17].

4) Increases Nitric Oxide

A study on 15 healthy men showed that those who received L-citrulline supplements had increased nitric oxide levels [18].

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 [19].

5) May Increase Blood Flow

A combination of L-citrulline and L-arginine supplements increased blood flow in the ears of rabbits [20].

A study of 10 healthy young men found that nitric oxide plays an important role in regulating blood flow [20]. Another study found that L-citrulline effectively increases nitric oxide [18, 19]. This suggests that L-citrulline may increase blood flow.

6) Decreases Blood Pressure

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 [21].

Another study of 12 healthy young men found that L-citrulline decreases both systolic and diastolic blood pressure [22].

7) Improves Heart Function

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 [14, 23].

A study of 35 patients revealed that L-citrulline improved the function of both the right and left ventricles as well as endothelial function [24].

8) May Increase Growth Hormone

A study on 17 cyclists revealed that L-citrulline increased growth hormone levels after exercise, but not at rest. This is most likely due to an increase in arginine levels. Arginine blocks the release of growth hormone inhibiting hormone [25].

9) May Boost 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 [26].

10) May Help Treat Sickle Cell Anemia

A study of 5 African-American patients with sickle cell anemia showed that L-citrulline supplementation may be a useful treatment 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 [27].

11) Helps Treat Urea Cycle Disorders

Urea cycle disorders are genetic disorders that impair the elimination of ammonia from the body [28]. L-Citrulline supplements can help treat urea cycle disorders by removing ammonia from the bloodstream and preventing a build-up of it [1].

Side Effects & Precautions

The most common side effect is stomach upset [24, 12].

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 supplements can be taken in different dosages, depending on what they are being used for.

For treating erectile dysfunction, 1,500 mg/day was proven to be an effective dosage [15].

To reduce fatigue and increase workout capacity, 2,400 mg/day was an effective dosage [13].

For heart failure, a dosage of 3,000 mg/day was effective [14].

To reduce blood pressure, 3,000 mg/day was effective in reducing blood pressure [22].

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 [29, 30].

User Experiences

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

Many people also report that L-citrulline is very helpful in regulating their blood pressure and maintaining their 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.

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About the Author

Will Hunter

BA (Psychology)
Will received his BA in Psychology from the University of California, Los Angeles. 
Will's main passion is learning how to optimize physical and mental performance through diet, supplement, and lifestyle interventions. He focuses on systems thinking to leverage technology and information and help you get the most out of your body and brain.

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