L-Citrulline and L-Arginine: This One-Two Amino Acid Punch Can Improve Circulation

Aging Youthfully

You have probably heard of the amino acid L-arginine, which is also called simply arginine.

It is well known in the nutrition science community for its ability to increase nitric oxide production resulting in a wide variety of health benefits. But you probably have not heard much about its powerful amino acid cousin, L-citrulline, or just citrulline.

If you eat at least six cups of watermelon every day then you’re getting an adequate dose of the amino acid citrulline. Citrulline’s name is actuallyFruits derived from the Latin word for watermelon—citrullus—because it was first isolated from the fruit in 1930.1

But you’re probably not eating six cups of watermelon every day, and actually it isn’t recommended. Watermelon is high in fructose (fruit sugar) and it’s a natural diuretic, so you’d be spending a whole lot of time in the bathroom. In addition to watermelon, citrulline is found in cucumbers and cantaloupe, at very low levels, as well as the milk protein casein. But since it is a nonessential amino acid, you don’t have to rely on getting citrulline from food. It is manufactured from other nutrients in your body, however, you only manufacture it if you are young and healthy and producing those other essential nutrients in adequate amounts!

The citrulline and arginine combination plays an essential role in your body

Citrulline, like arginine, is important in vasodilation, the widening of blood vessels, resulting from relaxation of smooth muscle cells within the vessel walls, especially in the large arteries and veins and smaller arterioles.

The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax. This results in a relaxing of the blood vessels, and increased blood flow.

In the body, citrulline is converted to the amino acid arginine, which goes on to make another important substance—nitric oxide. When citrulline enters the kidney, vascular endothelium and other tissues, it can be readily converted to arginine, thus raising plasma and tissue levels of arginine and enhancing nitric oxide production.2

The importance of nitric oxide to healthy blood flow

As stated, nitric oxide is integral to relaxing blood vessels which is necessary for healthy blood flow to the heart and genital area in both men and women, and throughout the body. Nitric oxide helps the blood vessels maintain their flexibility so that the blood flow is unrestricted. This, in turn, helps maintain healthy blood pressure, and a healthy sexual response.




When your vascular system is working efficiently there is less chance that a blood clot will form, which means there is less chance of having a heart attack or stroke.

Nitric oxide helps prevent blood clots because it prevents blood aggregation or platelets from becoming sticky. When platelets are not sticky they can move in a single file through the capillaries.

But if they are sticking together it’s like trying to move a dozen people through a crack in the wall. There is nowhere for the platelets to go, so a blood clot forms.

Additionally, nitric oxide works as an antioxidant that reduces the possibility of immune cells adhering to artery walls. This helps keep down inflammation, which most health professionals agree is a major cause of the plaque formation that contributes to atherosclerosis.

What inhibits adequate nitric oxide production?

  • People who have atherosclerosis, diabetes or hypertension (high blood pressure) often show impaired nitric oxide pathways.3
  • Over-consumption of salt can impair nitric oxide production.4
  • Aging—as we get older there is a decrease in nitric oxide production because the body makes less citrulline and arginine.5

Boosting nitric oxide production with nutritional supplements

Supplemental arginine helps the body produce more nitric oxide, and it helps with conditions that improve when blood vessels are relaxed, such as atherosclerosis and intermittent claudication (difficulty walking due to pain in leg muscles because of inadequate blood supply).

Even more importantly, new studies are showing that supplemental citrulline also assists in nitric oxide production by boosting blood levels of arginine. It does this because it is more readily absorbed and bioavailable than arginine alone, and it bypasses metabolism in the liver and gastrointestinal tract and is readily absorbed in the kidneys.6, 7

What to look for in a supplement

Citrulline is more effective at raising nitric oxide levels (in vascular endothelium) than arginine alone because approximately 50% of the arginine (when taken orally) gets converted into other amino acids by the intestines and the liver. Therefore, one should look for a citrulline supplement that also contains a small amount of arginine.

Taken together, you can get an immediate boost of nitric oxide production from the arginine, while allowing the citrulline time to produce additional arginine, for prolonged nitric oxide production.

This one-two punch of arginine and citrulline is a promising treatment for cardiovascular disease involving arginine deficiencies, reduced nitric oxide availability, and vascular dysfunction.

Together, citrulline and arginine supplementation is a natural and safe means of providing your body arginine, both short and long term. This combination can increase the natural production of nitric oxide, help reduce your chances of having a heart attack or stroke, boost your immune system, and improve your love live, all without the side effects of pharmaceutical drugs.


What does L-Citrulline and L-Arginine do?



This article is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a physician before embarking on a dietary supplement program.


  1. Collins JK, Wu G, Perkins-Veazie P, Spears K, Claypool PL, Baker RA, Clevidence BA. Nutrition. 2007 March.
  2. Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):275-90.
  3. Dessy, C.; Ferron, O. (2004). “Pathophysiological Roles of Nitric Oxide: In the Heart and the Coronary Vasculature”. Current Medical Chemistry – Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 3 (3): 207–216.
  4. Osanai, T; Fujiwara, N; Saitoh, M; Sasaki, S; Tomita, H; Nakamura, M; Osawa, H; Yamabe, H et al. (2002). “Relationship between salt intake, nitric oxide and asymmetric dimethylarginine and its relevance to patients with end-stage renal disease.”. Blood purification 20 (5): 466–8. doi:10.1159/000063555. PMID 12207094
  5. Kang L, Reyes RA, Delp, JM. Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2. Am J Physiol Heart Circ Physiol. 2009 September; 297(3): H1087–H1095. Published online 2009 July 17.
  6. Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr. 2007 Jun;137(6 Suppl 2):1646S-1649S.
  7. Romero M, Platt D, Caldwell R, Caldwell R. Therapeutic Use of Citrulline in Cardiovascular Disease. Cardiovascular Drug Reviews Vol. 24, No. 3–4, pp. 275–290.