Citrulline is a non-essential amino acid, meaning that 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 levels of arginine. Citrulline also plays a role in a physiological process called “the urea cycle,” in which toxic ammonia is converted to urea.
The body manufactures citrulline from the essential amino acid glutamine. Deficiency of citrulline is unlikely to occur.
A typical dose of citrulline is 6–18 grams daily. It is commonly sold in the form of citrulline malate.
There is little scientific support for any use of citrulline supplements.
Citrulline is most commonly marketed today as a supplement for enhancing sports performance. Based on exceedingly speculative reasoning, it is often described as an aerobic complement to the supplement creatine. Supposedly, citrulline enhances aerobic exercise capacity (relatively low-intensity exercise), while creatine enhances anaerobic exercise capacity (high-intensity exercise). However, while there have been numerous double-blind studies on creatine, available evidence on citrulline as a sports supplement is so scant that no conclusions whatsoever can be based on it.1,2 The only meaningful study reported thus far found that citrulline reduced rather than enhanced exercise capacity.4 Current enthusiasm for the supplement is therefore based entirely on testimonials. Since placebos increase sense of energy and well-being, and may even enhance performance, enthusiastic testimonials about a new and exciting supplement should be received with considerable caution.
Other proposed uses of citrulline are based on the fact that the body converts citrulline to the amino acid arginine. It is claimed by some that citrulline supplements are actually more effective at raising arginine levels than arginine supplements. However, this has not been established in any scientific sense. Furthermore, arginine itself is not a proven treatment for any condition. For example, citrulline is marketed as a treatment for impotence based on the assumption that arginine is effective for impotence. However, current evidence supporting arginine as an impotence treatment is weak at best, and citrulline itself has not been studied for this use in any meaningful way. Again, numerous testimonials are offered, but they mean little: placebos are very effective for impotence.
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.3 However, these studies were not conducted at the level of modern scientific standards, and have not been followed up.
As a naturally occurring amino acid, citrulline is believed to be safe. However, maximum safe doses in young children, pregnant or nursing women, or people with severe liver or kidney disease have not been established.
1. Bendahan D, Mattei JP, Ghattas B, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002;36:282–9.
2. Callis A, Magnan de Bornier B, Serrano JJ, et al. Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung. 1991;41:660–3.
4. Hickner RC, Tanner CJ, Evans CA et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006;38:660-6.
Last reviewed August 2013 by EBSCO CAM Review Board
Last Updated: 8/22/2013