What Is the Connection between Arginine and Citrulline?

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  • Written By: Marlene de Wilde
  • Edited By: O. Wallace
  • Last Modified Date: 24 October 2019
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Arginine and citrulline are non-essential amino acids with a bi-directional relationship. Citrulline can be produced from arginine through the action of nitric oxide synthase. Then it is converted back into arginine through the action of two other enzymes. This reverse interaction is important in the urea cycle and the production of nitric oxide.

Both arginine and citrulline are involved in the detoxification of ammonia through the production of urea. The synthesis of arginine takes place mainly in the intestinal and renal tracts where, through cellular action, citrulline is formed by the addition of ammonia to L-ornithine, which is then converted to arginine. Once the urea has been removed from the arginine, it converts back to ornithine. The amino acids in the urea cycle detoxify ammonia, which is a by-product of bacterial metabolism.

Arginine aids in the production of nitric oxide, which is a molecule essential for blood vessel dilation and so enables the healthy flow of blood through the body. Citrulline facilitates the production of arginine. As nitric-oxide boosting substances, both arginine and citrulline aid in the elimination of oxidative stress on the arteries and ease clogging or congestion. When blood is healthy and the heart does not need to work hard to pump it throughout the body, more energy is available for other tasks. Blood pressure decreases and the body can concentrate on defense and healing rather than surviving.


As a dietary supplement, arginine and citrulline can be taken in combination to support protein metabolism and maintain muscle tissue. For this reason, it is a popular supplement amongst bodybuilders. In addition, the combination of arginine and citrulline has been found to improve sexual dysfunction in men. Arginine alone is promoted as a health supplement to be used in the treatment of cardiovascular disease, as a growth supplement and as a treatment for erectile dysfunction.

Both arginine and citrulline are considered non-essential as they are produced within the body, but during times of stress such as growth, infection and trauma, synthesis of arginine may be affected and so supplements may need to be taken. Dietary sources of the amino acid include animal proteins, soy protein, nuts and eggs. Natural sources of citrulline include watermelon, cucumbers and the milk protein, casein; but as adequate amounts are produced by the body, it does not need to be consumed through diet except for rare cases of deficiency. The benefits of taking supplements are still debatable.


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