Citrulline Introduction

Citrulline is a classified nonessential amino acid that is, oddly, neither a component of any major proteins or enzymes. It provides for processes related to the production of energy in the body, and is responsible for the proper functioning of the immune system. Because of the nonessential nature of citrulline, it may not need to be consistently ingested from any dietary sources.

Citrulline is a very unusual amino acid. A variety of biological and chemical reactions define citrulline. This amino acid is formed in the urea cycle with the addition of carbon dioxide, forming ornithine. The process continues as ornithine is combined with aspartic acid to form arginosuccinic acid, which is then further metabolized to the most humanly bioavailable form, L-arginine.

This critical transformation, of citrulline to arginine, is fundamental for maintaining the homeostasis of certain toxicities within the body. Arginine itself is a key component in the formation of urea in the liver. The process of removing nitrogen metabolites from the body are directly dependant upon citrulline’s conversion to arginine. Citrulline, aspartic acid, citric acid, and magnesium work synergistically to remove excessive nitrogen build-up, and aid in the digestion, absorption, and metabolic processes of specific proteins.

Information concerning this amino acid remains scarce, and therefore not much scientific data is contained in this article.

Citrulline Food Sources

Because citrulline is made in great quantities from other amino acids in the intestinal tract and liver, a food graph is omitted. Persons should maintain a balanced diet from various whole food sources, as citrulline is naturally-occurring in various protein sources. Ensuring proper protein consumption may lessen the severity of illness, fatigue, and irritability (environmental stressors).

Citrulline Uses

Citrulline’s main function lies within its ability to provide for the detoxification process (es) of ammonia, and is, furthermore, essential for the excretion of oxidative waste processes in the human body via the urea cycle. [1] It is also responsible for the treatment of Ornithine Transcarbamylase, a urea cycle disorder. Urea cycle disorder is genetic disorder characterized by a deficiency of one of the enzymes needed to sustain the urea cycle. Citrulline is also critical in the improvement of deficiencies associated with the immune system and its overall functioning. The form of citrulline malate, or malic acid (a salt form of this amino acid), is found in abundance in many fruits and has been shown to enhance the effects of the main component, citrulline.

Malic Acid is a key component of the energy production yielded via the Kreb’s cycle. It conditions and assists lactate and pyruvate toward achieving a state of anabolism rather than catabolism. Supplementation of this nonessential amino acid has also lead to significant reductions of fatigue and an increase in energy production. [2] Citrulline has been shown to significantly increase the body’s metabolic rate, aerobic performance, and provide reductions in the onset of muscular fatigue. [3]

In conclusion, citrulline and citrulline malate supplementation may not only boost performance in physical activities, but may also provide our bodies with a means of eliminating the amino acid breakdown products of protein metabolism. It is considered equally important in the detoxification of ammonium and lactate from the blood.

Citrulline Dosages

Three to four grams, taken twice daily, have proven effective in various clinical applications concerning citrulline supplementation. Upon administration, results generally develop within a time period of 3 - 5 days.

The U.S. National Academy of Sciences recommends that healthy people achieve .36 grams of highly bioavailable protein for each pound of bodyweight - equaling 0.8 grams of protein, per kilogram of bodyweight.

Citrulline Toxicities and Deficiencies

Citrulline Deficiencies

Deficiencies of this amino acid are very rare. Those most susceptible to citrulline deficiency are; individuals suffering from rates of poor amino acid production in their livers (due to various ailments), and persons suffering from malabsorption conditions.. The elderly, young children (i.e. infants), sick or extremely malnourished persons are at an elevated risk for the development of deficiency.

There are some individuals that lack the enzyme needed to begin the biochemical process of converting citrulline into arginine. This results in a toxic build-up of citrulline within the body, often times leading to muscular fatigue, irritability, and mental confusion.

Citrulline Toxicities

Higher doses of citrulline can lead to a functional enzyme blockage in the urea cycle. This may stem from one consuming an excess of over 6 grams of citrulline per day, over an extended period of time. Symptoms of toxicity may include; nausea, diarrhea, and dizziness. These indicators last for duration of approximately one week.

Those suffering from toxicity are many times suggested to limit protein intakes, and advised to supplement with magnesium and zinc to assist in the problems associated with the urea cycle.


1. Balch, Phyllis A., James F. “Amino Acids.” Prescription for Nutritional Healing. Ed. Amy C. Tecklenberg. New York, NY: Penguin Putnam Inc., 3rd Ed. 2000. 42-53.

2. Bendahan D, Mattei JP, Ghattas B, et al. 2002. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med; 36(4):282-9.

3. Goubel F, Vanhoutte C, Allaf O, et al. 1997. Citrulline malate limits increase in muscle fatigue induced by bacterial indotoxins. Can J Physiol Pharmacol; 75(3):205-7.

4. Zest for life information page. “RDA of amino acids.” (1999-2003) (14 Sept. 2004).


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