L-Citrulline versus exhaustion

If you take the amino acid L-citrulline [structural formula shown below] in combination with intensive exertion you can postpone the moment of exhaustion. An animal study done by researchers at the University of Tsukuba demonstrated this, and the results have been published in the Journal of Nutritional Science and Vitaminology.


Endurance supplements which boost the production of nitrogen monoxide in the body are likely to contain amino acids like citrulline, arginine and ornithine. These amino acids stimulate the urea cycle, a process that removes broken down proteins and ammonia from the body. As the concentration of ammonia in the blood rises, the body becomes tired. This is one of the factors in fatigue.

The researchers did an experiment lasting a week with mice. Half of the mice were given 250 mg L-citrulline per kg bodyweight every day. The human equivalent of that dose is approximately 1.5-2.5 grams.

On days 1, 3 and 5 the mice had to swim for 10 minutes in an aquarium. They had a weight attached to their tail so the exertion was greater. On day 7 the animals had to swim to the point of exhaustion.

The figure below shows that the mice that had been given the supplement swam for almost 10 minutes longer. After the exhaustion test the mice in the citrulline group had less ammonia in their blood, but also less lactic acid. That indicates that they were more thrifty with their glucose burning. In addition, the mice in the citrulline group had more glycogen in their muscle cells.








“Our present findings suggest that citrulline supplementation would be very helpful for individuals performing high intensity exercise”, the Japanese conclude.

The researchers were not on the payroll of a supplements manufacturer or a raw materials producer. The Japanese government funded the research.

Effects of citrulline supplementation on fatigue and exercise performance in mice.


During high-intensity exercise, the concentration of ammonia is augmented in skeletal muscle. Ammonia activates phosphofructokinase and prevents oxidation of pyruvate to acetyl CoA, thus leading to exhaustion. Citrulline is an amino acid component of the urea cycle in the liver, along with ornithine and arginine. The aim of this study was to examine the effect of citrulline supplementation on fatigue and performance during high-intensity exercise. We constructed a swimming exercise protocol, in which mice were subjected to exhaustive swimming with a load of 5% body weight, and measured the time until exhaustion, the blood levels of lactate and ammonia, and the glycogen content of the gastrocnemius and biceps femoris muscles. Citrulline supplementation significantly increased the swimming time until exhaustion. Exercise-induced blood ammonia elevation was repressed by citrulline supplementation, and exercise-induced blood lactate increment in the citrulline-supplemented group was significantly lower than that in the non-supplemented group. Citrulline supplementation may facilitate the detoxification of ammonia via the urea cycle and inhibit additional glycolysis. Our findings suggest that citrulline supplementation may be useful for improving the exercise performance of athletes.

PMID: 21908948 [PubMed – indexed for MEDLINE]

Source: http://www.ncbi.nlm.nih.gov/pubmed/21908948