What Is Citrulline?

For the Treatment of Sickle Cell Disease, Heart Health and More

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Verywell / Anastasia Tretiak

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Citrulline is a non-essential amino acid that is made in the liver and intestine, but some individuals may take it as a natural supplement for various health and athletic benefits. It can also be found in foods like watermelon.

Its function is to detoxify ammonia, a waste product, and act as a vasodilator (dilating the blood vessels). Citrulline is also said to have an antioxidant effect.

There are two forms of citrulline supplements. Understanding the difference between citrulline malate vs. l-citrulline supplements can help you decide which one you'd prefer to use. L-citrulline is citrulline without any other substance. Citrulline malate is made up of L-citrulline and DL-malate, which may help with blood flow and energy conversion.

Also Known As

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

Citrulline Benefits

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

What Research Says About Citrulline Benefits

Athletic Performance

A 2010 study involving 41 men found 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)
  • A 40% decrease in muscle soreness after exercise

Researchers note that citrulline malate may be useful in increasing athletic performance and may reduce soreness that can occur after exercising.

Another study, published in 2017, looking at older individuals found that citrulline modestly increased muscle blood flow during certain types of exercise in men but not in 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-citrulline use can lower blood pressure in adults with hypertension (high blood pressure) and those with pre-hypertension. These studies suggest that pharmaceutical-grade L-citrulline was helpful in promoting heart health.

A paper published in 2019 reviewed 8 trials looking at adults. They found that citrulline can lower systolic blood pressure (by 4 mmHg). A significant decrease in diastolic blood pressure was seen only at higher doses. The authors recommended a diet rich in citrulline-containing foods to help prevent hypertension.

It’s important to note that there are several grades of supplements that may be less effective (such as medical grade, nutritional grade, and cosmetic grade).

The pharmaceutical grade must be more than 99% pure (from natural sources) and must contain no dyes, filler, binder, or unknown substances.

Erectile Dysfunction

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 individuals who took it, as compared to improvement in 8.3% of those who took a fake treatment.

The researchers concluded that L-citrulline was less effective than drugs like Viagra. However, it was concluded to be safe and well-accepted by individuals who tried it for this condition.

L-citrulline is said to boost L-arginine, which in turn helps to raise nitrogen oxide (NO) production. NO promotes the relaxation of blood vessels, resulting in oxygen-rich blood moving 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.

Sickle Cell Disease

Studies have shown that a twice-daily dose of L-citrulline by mouth may relieve some symptoms of a blood disorder called sickle cell disease. Those in the study reported better blood health and an overall improvement in their well-being.

Another study found that promoting L-arginine levels via L-citrulline supplements may help decrease pain associated with sickle cell anemia (a type of sickle cell disease). This study found that L-arginine supplementation may boost the treatment of sickle cell anemia, but more research is needed to evaluate the long-term safety and efficacy of these natural supplements.

What Does Citrulline Do in Your Body?

In the body, L-citrulline is transformed into a different amino acid, called L-arginine. This 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).

What Are the Side Effects of Citrulline?

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

Contraindications

Contraindications for L-citrulline include:

  • Pregnancy: There is not enough clinical research to prove the safety of citrulline during pregnancy.
  • Breastfeeding: There is not enough clinical research to prove the safety of citrulline during breastfeeding.

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

  • Phosphodiesterase-5 inhibitors (PDE5-Inhibitors): PDE5-inhibitors include erectile dysfunction drugs like Viagra. Both L-citrulline and PDE5-inhibitors can lower blood pressure, and the combination of these two medications can cause low blood pressure.
  • Nitrates: Taking nitrate medications, which increase blood flow to the heart, along with citrulline may result in an increase in blood flow to the heart that could cause side effects. Nitrate drugs include Dilatrate-SR and Isordil (isosorbide dinitrate), ISMO (isosorbide mononitrate), and Nitro-Dur, Nitrolingual or Nitrostat (nitroglycerin).
  • 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, along with citrulline may cause blood pressure to drop too low.

Other prescription medications could interact with citrulline, so its use should always be discussed with your healthcare provider.

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

Citrulline powder
Verywell / Anastasia Tretiak

Citrulline Dosage

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 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.

What to Look For

Natural supplements, such as citrulline, are not regulated by the Food and Drug Administration (FDA). 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
  • ConsumerLab.com

These organizations evaluate and report on a product’s level of safety, purity, and potency.

Frequently Asked Questions

  • How can I get citrulline in my daily diet?

    Some of the best sources of citrulline from food include:

    • Watermelon
    • Bitter gourd and other gourds
    • Squash
    • Nuts
    • Chickpeas
    • Pumpkin
    • Cucumbers
  • Which type of melon is known to have the very highest level of citrulline?


    Watermelon, specifically, Crimson Sweet and Dixielee watermelon, has the highest levels of citrulline.

  • Does citrulline increase testosterone?

    Research hasn't linked citrulline to an increase in testosterone.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Johnson, S. L-Citrulline. U.S. Food & Drug Administration. Pharmacy Compounding Advisory Committee Meeting 2017, November 20.

  2. Pérez-guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215-22. doi: 10.1519/JSC.0b013e3181cb28e0

  3. Allerton TD, Proctor DN, Stephens JM, Dugas TR, Spielmann G, Irving BA. L-citrulline supplementation: Impact on cardiometabolic health. Nutrients. 2018;10(7) doi:10.3390/nu10070921

  4. Cormio L, De siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011;77(1):119-22. doi: 10.1016/j.urology.2010.08.028

  5. Waugh WH, Daeschner CW, Files BA, Mcconnell ME, Strandjord SE. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. J Natl Med Assoc. 2001;93(10):363-71.

  6. Eleutério RMN, Nascimento FO, Araújo TG, et al. Double-blind clinical trial of arginine supplementation in the treatment of adult patients with sickle cell anaemiaAdvances in Hematology. 2019;2019:1-6. doi:/10.1155/2019/4397150

  7. Moinard C, Nicolis I, Neveux N, Darquy S, Bénazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008;99(4):855-62. doi:10.1017/S0007114507841110

  8. Hartman, J. Wehner, T, et al. Citrulline and arginine content of taxa of Cucurbitaceae. Journal of Horticulturae. 2012; vol:5 Iss.1. doi:10.3390/horticulturae5010022

Additional Reading

By Sherry Christiansen
Sherry Christiansen is a medical writer with a healthcare background. She has worked in the hospital setting and collaborated on Alzheimer's research.