All about citrulline: a closer look at an amino acid

Citrulline is a nonessential amino acid that was first isolated from watermelon in 1914. It is named for the Latin word for watermelon, Citrullus vulgaris. It plays an important role in the urea cycle, also called the ornithine cycle, and in the production of nitric oxide in the body.

Can humans produce citrulline themselves?

The human body can produce the amino acid itself in a variety of ways:

In the urea cycle: Citrulline is an important intermediate in the ornithine cycle, which takes place in the liver. This cycle serves to convert nitrogenous waste products into urea, which can then be excreted by the kidneys [1].

From L-Arginine: The body can produce citrulline from the amino acid L-arginine.

From ornithine: In the ornithine cycle, ornithine is converted to citrulline [3].

Citrulline-NO cycle in the cytosol: Citrulline is formed as a by-product during the formation of nitric oxide (NO) by NO synthase in the cytosol of cells, not in the mitochondria. In this reaction, arginine is converted to citrulline and NO [4].

In certain organs: In addition to the liver, other organs such as the kidneys and small intestine also produce the important amino acid [5].

Although the human body can produce citrulline itself, it does not always produce it in sufficient quantities. In certain situations, for example during increased physical exertion or illness, the body's own production of the amino acid may be insufficient. In such cases, it should be taken as a dietary supplement after consulting a doctor, for example as a powder. Those for whom citrulline powder is too much effort can opt for tablets or capsules.  

What are the natural sources of citrulline?

Citrulline is found in a variety of foods, with watermelon being the most abundant natural source. Other foods containing citrulline include:

• Pumpkins
• Cucumbers
• Melons
• Bitter melons
• Pumpkin seeds
• Soy products

Is there a difference between citrulline and L-citrulline?

There is no difference between citrulline and L-citrulline. L-citrulline is the more precise designation, which refers to the specific spatial orientation (L-form) of the molecule. 

Important bodily functions:

Nitric oxide production: One of the main functions of L-citrulline in the body is its role in the production of nitric oxide (NO). It is converted into arginine or L-arginine in the body, which in turn contributes to the production of NO. Nitric oxide is an important vasodilator that widens blood vessels and thus improves blood flow. [6]

Urea cycle: The ornithine cycle, a biochemical process in which the body converts toxic ammonia into urea, also involves the amino acid. This process is crucial for detoxifying the body and maintaining a healthy nitrogen balance. [7]

The effect of L-citrulline: when should you take the non-essential amino acid?

Because the conversion of L-citrulline to arginine in the body happens with a time lag, this leads to more arginine being present in the blood over a longer period of time. This means that the body can benefit from the effect of arginine for longer. The effect of citrulline or its effect on the body is manifold:

Enhancement of athletic performance
L-citrulline has shown great promise in studies on improving athletic performance. It can increase endurance, delay fatigue and boost muscle strength. This is mainly attributed to the improved blood flow caused by L-arginine and the increased oxygen transport to the muscles. [8]

Blood pressure regulation and improved blood flow
Some studies suggest that a regular intake of L-citrulline or L-arginine can lower blood pressure in people with hypertension. [9]

Heart health support
L-citrulline's blood pressure-lowering and vasodilatory effects may also contribute to overall heart health and a healthy cardiovascular system. It can reduce the strain on the heart and potentially reduce the risk of cardiovascular disease. [10]

Dosage and administration of L-citrulline

The optimal dosage of citrulline can vary depending on your individual needs, goals and desired effect – depending on whether the amino acid is taken to improve athletic performance or for health purposes. In addition to powder, supplements with the amino acid are also available in tablet form. 

Does L-citrulline have any side effects?

L-citrulline powder and capsules are generally considered safe when not overdosed. However, side effects such as stomach problems or bloating are possible.

People with certain health conditions should consult a doctor before taking supplements containing L-citrulline:

• Pregnant and breastfeeding women
• People with kidney disease
• People taking antihypertensive medication
• Patients with cardiovascular disease

Are supplements with L-citrulline or L-citrulline malate vegan?

Supplements with L-citrulline and L-citrulline malate, whether in powder or tablet form, can be vegan. Originally, the amino acid was discovered in high concentrations in the skin of watermelons and is also found in other cucurbits, which are naturally vegan. However, it is usually produced synthetically for use in dietary supplements by converting the amino acid arginine.

There are usually two different forms of dietary supplements available as a powder or capsule, containing either pure L-citrulline or L-citrulline malate, which is a combination of the amino acid and malate. Malate is malic acid. The 2:1 ratio of L-citrulline malate is the most common form of L-citrulline malate used in sports supplements because the combination with malate offers higher bioavailability and additional benefits in energy production and the reduction of muscle fatigue after exercise. If you are not sure which citrulline content is best for you and whether you should choose a product with or without malate, it is best to talk to your doctor. Also, when choosing supplements with citrulline malate, make sure they are of high quality. 

Increase physical performance

The amino acid L-citrulline offers a wide range of potential health benefits, from improving performance in sports to supporting cardiovascular health. However, as with all dietary supplements, whether with vitamin D3, omega 3, vitamin C, etc., it is advisable to consult a health professional before taking them and to discuss the exact dosage.

Sources:

[1] https://flexikon.doccheck.com/de/Harnstoffzyklus
[2] https://www.opendata.uni-halle.de/bitstream/1981185920/8437/1/Doktorarbeit_Helen%20Sterz.pdf
[3] https://www.spektrum.de/lexikon/biologie-kompakt/harnstoffzyklus/5275
[4] https://dermaviduals.de/deutsch/entzuendliche-hauterkrankungen-durch-oxidativen-und-nitrosativen-stress.html
[5] https://www.aesan.gob.es/seguridad_alimentaria/evaluacion_riesgos/FOOD_SUPPLEMENTS_4.pdf
[6] https://doi.org/10.3390/nu11071679
[7] https://flexikon.doccheck.com/de/Harnstoffzyklus
[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073798/
[9] https://pubmed.ncbi.nlm.nih.gov/31336573/
[10] https://doi.org/10.3390/nu11071679