Although the use of amino acids in sports nutrition is quite commonplace, you’re probably not familiar with L-citrulline. But as Andrew Hamilton explains, some recent research suggests that this little known nutrient may have real potential to enhance your sport performance.


Think of performance-boosting foods and watermelon is unlikely to be top of your list. However, watermelon is rich in an amino acid called L-citrulline (referred to from here on simply as citrulline). The name citrulline is derived from citrullus, which is actually the Latin word for watermelon. Although we normally think of amino acids as the building blocks of protein, citrulline is not used to build structural proteins in the body. It’s also a non-essential amino acid, which means that when conditions are right, your body can make it from other compounds. However, just because it’s non-essential and uninvolved in muscle building doesn’t mean that citrulline is unimportant.

Citrulline in the body

When it comes to the potential to enhance sport performance, citrulline plays two key roles in the body. One of these is to help the body excrete a toxic by-product of metabolism called ammonia. This is important because any accumulation of ammonia in exercising muscles can impair exercise performance.

Another way that citrulline could help enhance performance is because it can be converted in the body to another amino acid called arginine. Why is this important? Well, scientists now know that arginine can readily be used in the body to make a key signalling molecule called nitric oxide, which has the ability to increase blood flow through muscles, providing potential benefits during exercise. Indeed the use of nitrate supplements such as beetroot juice to enhance exercise performance works by using this exact same principle.

Performance evidence from citrulline

Sports scientists first became interested in citrulline when they noticed that consuming citrulline could raise nitric oxide levels in the body. Sports supplements claiming to boost performance by raising levels of nitric oxide are nothing new, but many such products have been shown to be ineffective both at raising nitric oxide levels or boosting performance – most likely due to the fact they focussed on arginine as the key ingredient (see box below). The current weight of evidence in favour of citrulline use however is a good deal stronger.

Although there had previously been quite a few animal studies into citrulline, one of the earliest positive studies into citrulline supplementation to enhance performance in humans looked at the effects of a single dose of citrulline before high-intensity resistance exercise. The study used a randomised, double-blind, crossover design (the most rigorous kind) with a relatively large number of subjects, making its results significant. When the subjects took an 8g dose of citrulline malate beforehand, they were able to perform more sets and more reps (53% more than when they took a placebo). Another benefit was that during the 48 hours following the resistance exercise, the subjects reported a significant decrease in muscle soreness of up to 40%.

Another study looked at the effects of giving 6g of citrulline malate two hours before a 137km cycling stage. This study however did not look at performance per se, but rather if giving citrulline could aid recovery or affect other aspects of metabolism. The results showed that when the cyclists took the citrulline, they experienced a greater rise in growth hormone after the ride – a good thing since growth hormone helps stimulate post-exercise muscle recovery and growth. The citrulline also seemed to enhance the cyclists’ muscles ability to use branched chain amino acids (BCAAs) as fuel during exercise. This is significant because we know that BCAAs are a valuable source of energy during prolonged and vigorous exercise and we also know that a greater availability of BCAAs during exercise may help to reduce muscle damage and soreness following that exercise.

Why citrulline, and not arginine?

If arginine can be readily converted to nitric oxide, why not just consume extra arginine instead of citrulline? The answer is to do with the way arginine is (or actually isn’t) absorbed. When you consume arginine – either in food or in supplemental form – that arginine is readily absorbed from the intestines into the bloodstream. The problem arises however when the blood passes through the liver because much of the arginine in the blood is broken down by an enzyme called arginase. This is a normal and natural process as part of the urea cycle, in which the body rids itself of protein breakdown products. However, when you’re trying to boost nitric oxide production in the body, this liver barrier is something of a problem.

Taking citrulline orally however bypasses this barrier; ingested citrulline passes through the liver unaffected, meaning it can be transported in tissues all over the body and then converted to arginine (resulting in increased nitric oxide production) wherever needed. Indeed, taking citrulline is more effective at raising tissue arginine than taking arginine itself. It also explains why the evidence for citrulline supplementation is far more convincing in terms of boosting nitric oxide than many of the so-called nitric oxide boosting sports supplements, which have tended to be based on arginine products.


Of mice and men!

When it comes to human performance, it’s risky to draw firm conclusions from animal studies. Nevertheless, when combined with findings from human studies, a 2011 study on mice provides compelling evidence that citrulline really might have something going for it. Japanese researchers examined the effect of citrulline supplementation on the fatigue and performance of mice that swam to exhaustion while carrying a weight on their tail equivalent to 5% of their own bodyweight. As shown to the right, the mice that had been given citrulline managed an average swimming time of 25 minutes. This compared to just 15 minutes with the mice given an inert placebo! Giving citrulline also helped to suppress the rise in exercise-induced blood lactate, which causes muscle fatigue and (eventually) forces the muscle to stop (see graphic right). The researchers were unequivocal in their conclusions commenting: “Our findings suggest that citrulline supplementation may be useful for improving the exercise performance of athletes.”

The very latest research

Coming right up to date, the evidence in favour of citrulline as an ergogenic nutrient continues to look positive. A study published in September of last year investigated the effects of citrulline supplementation on exercise performance, blood lactate, heart rate and blood pressure during lower-body resistance exercise. Twelve resistance-trained male subjects were randomly assigned to take either an inert placebo or 8g of citrulline prior to exercise. The resistance training consisted of five sequential sets (at a weight equivalent to 60% of 1rep maximum) performed to failure on the leg press, hack squat, and leg extension machines. The results showed that the subjects in the citrulline-supplemented group were able to perform significantly higher numbers of repetitions during all three exercises, with the researchers concluding that: “Citrulline supplementation may be beneficial in improving exercise performance during high-intensity resistance exercise.”

Happy tummies

Although much of the research on citrulline has concentrated on enhancing exercise performance, a recent study suggests that citrulline could help those who suffer with sensitive tummies during sport. Splanchnic hypoperfusion (SH) is a condition where the normal patterns of blood flow to the intestines and organs in the abdominal region are disturbed for example during vigorous exercise, when blood is directed away from the abdominal region to supply the working muscles with more blood (and oxygen). This leads to a range of gastrointestinal symptoms such as cramps and nausea, which can severely dent your performance. The good news is that recent research suggests citrulline can help to reduce the incidence of SH in athletes. In a randomised, double-blinded crossover study (the most scientifically rigorous of the lot), 10 men cycled for 60 minutes on two separate occasions at 70% of their maximum workload (moderately hard) after taking 10g of L-citrulline or an inert placebo. During both trials, the blood flow to the gut was assessed and a technique known as “sugar probing” was used to monitor the changes in gut permeability and levels of intestinal damage.

When the subjects took the citrulline, the blood flow to the gut was unaltered during exercise (i.e. SH was prevented) and there was no indication of increased damage to the intestine. When they took the placebo however, SH was observed in the subjects, which was also accompanied by increased markers of intestinal damage. How did the citrulline exert its protective effect? The most likely explanation is that when converted to arginine in the gut region, the production of nitric oxide was increased, and since nitric oxide increases blood flow in small blood vessels, this helped to offset any tendency towards SH.



As with any new area of research, more studies will be needed before we can fully understand how to get the best from citrulline – for example, determining the optimum dose, when it should be taken, whether it’s equally effective in all individuals, and whether there are any drawbacks to citrulline supplementation. In the meantime however, recent evidence from both animal and human studies suggests that citrulline may be able to enhance high-intensity exercise performance, and may also help prevent cramps and nausea in those athletes who are prone to gut problems during exercise. If you fancy giving citrulline a try the box out right provides some practical recommendations.

Practical recommendations

  • The evidence to date suggests that taking 8g of citrulline (as malate) a couple of hours or so before high-intensity exercise could enhance performance. This is probably a good starting point to experiment with.
  • The evidence that citrulline can enhance performance during more moderate intensity training is weaker and therefore supplementation less recommended.
  • The cheapest way to take citrulline is as a pure citrulline malate powder dissolved in water – capsules of citrulline tend to be very expensive.
  • Citrulline is a generally safe supplement – however, you should NOT take citrulline if you’re pregnant, breast feeding, taking any drug for erectile dysfunction such as Viagra or you use nitrate supplementation products such as beetroot juice before exercise.

WORDS: Andrew Hamilton

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