Citrulline

Geschatte leestijd: 6 minuten Citrulline is used as a supplement as a so-called ‘NO-Booster’. In this article, we will discuss the operation of ‘NO-Boosters’ in general and the functioning of citrulline in particular. We also compare its functioning with that of another popular NO-Booster, arginine.

No Boosters and arginine

To explain the effect of citrulline, we first need to discuss arginine. Arginine is known as a so-called NO-Booster. “NO” here stands for Nitric (mon)Oxide, nitrogen monoxide. NO plays a role, among other things, in dilating vessels thereby increasing blood supply and moving more oxygen, for example to the muscles for more energy. In an earlier article about NO-Boosters, I described research that showed arginine is largely broken down before it can do its job after oral intake. Although arginine works as a NO-Booster in the body, you may wonder if this effect is actually achieved with oral intake of arginine.

What is Citrulline?

Citrulline is a so-called precursor of arginine; it can be converted into arginine in the body. Citrulline could be a more interesting alternative because it increases the production of arginine in the body itself [2,3]. Unlike arginine, it is not broken down by arginase enzymes. As a result, about 80% of the citrulline is converted into arginine in the kidneys [3].

Citrulline Malate

Several supplements are offered in the malate form. Malate is the salt form of malic acid, which gives fruits their sour taste. Malate plays a role in the Krebs cycle, or “citric acid cycle,” where it plays a role in energy supply [4,5]. The addition of malate to supplements such as creatine, but also citrulline would increase their effectiveness. The combination of citrulline and malate would thus offer various benefits. The previously mentioned increase in arginine [6], but also the lowering of lactic acid and ammonia [7,8,9].

“Citrulline increases maximum number of repetitions in leg training”

A 2010 study showed that the use of 8 grams of citrulline malate prior to a chest workout allowed for more repetitions to be done during bench presses and incline flyes (see further) [10]. Since the legs contain more muscle mass and pose a greater burden on metabolism, American researchers in 2014 wanted to look at the effect on the lower body [1]. They measured the effects of citrulline malate on performance during five different leg exercises, but also on lactic acid production, heart rate, and blood pressure. For this, they divided 12 experienced strength athletes into two groups (actually 14, but two dropped out with injuries incurred outside the study).

• Group 1 received 8 grams of citrulline malate
• Group 2 received a placebo (made of maltodextrin and aspartame)

An hour later, they did a short warm-up on the bike followed by the training protocol: Five sets to muscle failure in three different exercises – leg press, hack squat, and leg extension. So, five times as many repetitions as possible per exercise. A weight was chosen that was 60%1RM. This is 60% of the maximum weight with which they could do one repetition. This had been determined seven days earlier. Before and after, the aforementioned values such as heart rate, the amount of lactic acid in the blood, and blood pressure were measured. Seven days later, the groups were switched and the placebo group received citrulline malate and vice versa. As expected, in every exercise, the number of repetitions per set decreased due to fatigue. However, in the group that received citrulline malate, more repetitions were performed in all three exercises than in the placebo group. In all measurements for heart rate, blood pressure, and lactic acid, however, no significant differences were found.

In conclusion, our results suggest that citrulline malate supplementation may be beneficial in improving exercise performance during lower-body multiple-bout resistance exercise in advanced resistance trained men. B. Wax, Mississippi State University

Better performance through citrulline malate, but unclear why

As said, citrulline malate increased the maximum number of repetitions. However, the researchers do not see why. The expected effects on blood pressure, lactic acid, and ammonia were absent. If vessels dilate, it means that the same amount of blood flowing through them encounters less resistance. Blood pressure should then be lower. The researchers therefore conclude:

further research is necessary to determine which mechanism may be directly attributed ergogenic effects occurring during resistance training protocols. B. Wax, Mississippi State University

Citrulline malate and athletic performance according to previous research

That citrulline malate can improve performance has been demonstrated in various previous studies. Citrulline malate achieves this on multiple levels.

More endurance

According to, among other research from 2002, citrulline malate provides more endurance [4]. Citrulline malate was found to increase the production of ATP (Adenosine Triphosphate, fuel for the muscles) by 34%. The production of phosphocreatine needed to make new ATP was increased by 20% during rest. That this is important is apparent alone from the fact that one of the most popular supplements worldwide, creatine, is aimed at increasing ATP by making more phosphocreatine available. The same study showed that the fatigue, as experienced by the participants, was significantly lower when citrulline malate had been taken.

More muscle strength through citrulline

In a Spanish study from 2010, the maximum number of repetitions and muscle strength during bench pressing with a resistance/weight of 80%1RM and incline flyes with 60%1RM [10] were examined in a similar manner as the 2014 study. Eight sets were done showing that the intake of citrulline malate allowed for a higher number of repetitions to be done. Moreover, the participants had less muscle soreness afterward (a sign of faster recovery) when citrulline malate (CM) was taken.

We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve post-exercise muscle soreness. Thus, athletes undergoing intensive preparation involving a high level of training or in competitive events might profit from CM. Pérez-Guisado, University of Córdoba

Citrulline malate and BCAAs

Now, you can often expect a caveat from my articles in the sense that I show studies that show no positive effect or even a negative effect. However, in this case, I couldn’t find such caveats/not many. Instead, I found several other positive studies showing that muscles work more efficiently through citrulline malate [8] and that more growth hormone is produced [11]. From the last-mentioned study that showed an increase in growth hormone, it also appeared that more Branched Chain Amino Acids (BCAAs) are used to provide energy. In short, they are very important building blocks for the muscles. In the study from which this consumption appeared, no strength training was done, but almost 3 hours of cycling was performed. As a cyclist, you are then glad that the amino acids in the muscles are used as much as possible for energy to be able to cycle longer or faster. If it’s about muscle mass then you don’t want this. Because the study was done under these circumstances, it says nothing about the consumption of amino acids (in particular BCAAs) during strength training.

Muscle growth with citrulline?

I also can’t find articles that, for example, have looked at protein synthesis or other indicators of muscle growth under the influence of citrulline malate. With more energy and more repetitions during training, you would think there is a greater anabolic stimulus, the stimulus for the muscles to grow. If this energy, however, is partly taken from the building blocks for the muscles, it is questionable whether this translates into more muscle mass. If it’s purely about performance at the moment, both in terms of muscle strength and condition, citrulline malate seems to be recommended. References

1. Wax, Benjamin (PhD); Kavazis, Andreas N. (PhD); Weldon, Kevin (MS); Sperlak, Joseph (MS). Effects of Supplemental Citrulline Malate Ingestion During Repeated Bouts of Lower-body Exercise in Advanced Weight Lifters.Journal of Strength & Conditioning Research: Post Acceptance: September 15, 2014
2. Jabecka A, Ast J, Bogdaski P, Drozdowski M, Pawlak-Lemaska K, Cielewicz AR,Pupek-Musialik D. Oral L-arginine supplementation in patients with mild arterial hypertension and its effect on plasma level of asymmetric dimethylarginine,L-citruline, L-arginine and antioxidant status. Eur Rev Med Pharmacol Sci. 2012 Nov;16(12):1665-74. PubMed PMID: 23161038.
3. van de Poll MC, Soeters PB, Deutz NE, Fearon KC, and Dejong CH. Renal metabolism of amino acids: its role in interorgan amino acid exchange. Am J Clin Nutr 79: 185-197, 2004.
4. Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, and Cozzone PJ. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med 36: 282-289, 2002.
5. Wagenmakers AJ. Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. Exerc Sport Sci Rev 26: 287-314, 1998.
6. Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, and McCammon M. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 38: 660-666, 2006
7. Briand J, Blehaut H, Calvayrac R, and Laval-Martin D. Use of a microbial model for the determination of drug effects on cell metabolism and energetics: study of citrulline-malate. Biopharm Drug Dispos 13: 1-22, 1992
8. Giannesini B, Le Fur Y, Cozzone PJ, Verleye M, Le Guern ME, and Bendahan D. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol 667: 100-104, 2011.
9. Verleye M, Heulard I, Stephens JR, Levy RH, and Gillardin JM. Effects of citrulline malate on bacterial lipopolysaccharide induced endotoxemia in rats. Arzneimittelforschung 45: 712-715, 1995.
10. Perez-Guisado J and Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 24: 1215-1222, 2010.
11. Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons A. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010 Sep;110(2):341-51. doi: 10.1007/s00421-010-1509-4. Epub 2010 May 25. PubMed PMID: 20499249.