Citrulline as a therapeutic supplement

DEFINITION: A natural substance of the human body used as a supplement to treat specific health conditions.

• PRINCIPAL PROPOSED USE: Enhancing sports performance
• OTHER PROPOSED USES: Alzheimer’s disease, fatigue, male sexual dysfunction, reducing blood pressure, heart disease, sickle cell disease, muscle wasting

Overview

Citrulline is a nonessential amino acid, meaning the body can manufacture it from other nutrients. Within the body, citrulline is converted to the amino acid L-arginine. Some of the proposed uses of citrulline supplements are based on raising arginine levels. Citrulline also plays a role in a physiological process called the urea cycle, in which toxic ammonia is converted to urea.

Requirements and Sources

The body manufactures citrulline from the essential amino acid glutamine. A deficiency of citrulline is unlikely to occur. Citrulline can be found in sources such as watermelon.

Therapeutic Dosages

A typical dose of citrulline is 6 to 18 grams daily. It is commonly sold as citrulline malate.

Therapeutic Uses

The proposed uses of citrulline are based on the fact that the body converts citrulline to the amino acid arginine. Some claim that citrulline supplements are more effective at raising arginine levels than arginine supplements. Emerging scientific studies in the twenty-first century also indicate citrulline may be effective in treating specific medical conditions. Two studies found that supplementation with citrulline improved erectile function in men. Although these studies were on a smaller scale, they indicate citrulline may hold promise for improving erectile function and sexual satisfaction.

Emerging studies attesting to citrulline's effectiveness have allowed it to attain popularity in certain athletic communities, such as among bodybuilders. Many enthusiasts are attracted to claims of its ability to enhance performance, where even a slight advantage can be consequential. Scientific research has increasingly supported claims that citrulline may increase blood flow to muscles, reduce fatigue, and improve endurance.

Very preliminary studies conducted in France in the late 1970s hint that citrulline may improve mental function in people with Alzheimer’s disease and also reduce general fatigue. However, these studies were not conducted at modern scientific standards. Studies have indicated that citrulline may help reduce blood pressure by increasing nitric oxide production and improving blood vessel function. Other conditions believed to receive benefits from citrulline supplementation include sickle cell disease, muscle wasting, diabetes, cognitive impairment, and intestinal problems.

Safety Issues

As a naturally occurring amino acid, citrulline is believed to be safe. However, maximum safe doses in young children, pregnant or nursing women, and people with severe liver or kidney disease have not been established. Prospective consumers should understand that, as a supplement, citrulline is not a drug regulated by the Food and Drug Administration. As such, citrulline is not tested for safety or effectiveness. It falls upon the consumer to consult with healthcare providers over potential side effects or whether the supplement will have the effect for which they are paying.

Bibliography

Bendahan, D., et al. "Citrulline/Malate Promotes Aerobic Energy Production in Human Exercising Muscle." British Journal of Sports Medicine, vol. 36, 2002, pp. 282-9.

Cormio, Luigi, et al. "Oral L-Citrulline Supplementation Improves Erection Hardness in Men with Mild Erectile Dysfunction." Urology, vol. 77, no. 1, 2011, pp. 119-22, doi.org/10.1016/j.urology.2010.08.028. Accessed 14 Dec. 2025.

Hickner, R. C., et al. "L-citrulline Reduces Time to Exhaustion and Insulin Response to a Graded Exercise Test." Medicine and Science in Sports and Exercise, vol. 38, 2006, pp. 660-6.

"L-arginine." Mayo Clinic, 28 June 2025, www.mayoclinic.org/drugs-supplements-l-arginine/art-20364681. Accessed 14 Dec. 2025.

Lefton, Jennifer. "Benefits of Citrulline and Whether It’s Safe to Take" Verywell Health, 11 Dec. 2025, www.verywellhealth.com/citrulline-4774848. Accessed 14 Dec. 2025.

Miller, Kelli. "L-citrulline: Uses and Risks." WebMD, 13 Aug. 2025, www.webmd.com/vitamins-and-supplements/l-citrulline-uses-and-risks. Accessed 14 Dec. 2025.

Vårvik, Fredrik Tonstad, et al. “Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis.” International Journal of Sport Nutrition and Exercise Metabolism, vol. 31, no. 4, 2021, pp. 350–8. Accessed 14 Dec. 2025.

"What is Citrulline?" Cleveland Clinic, 7 Feb. 2023, health.clevelandclinic.org/citrulline-benefits. Accessed 14 Dec. 2025.