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In the competitive arena of sports, athletes are continuously seeking training aids and supplements that may provide them with a competitive edge. Substances that increase athletic performance (i.e., enhanced muscular power, strength, and endurance) are referred to as ergogenics. Recently, studies reported that an over-the-counter supplement named citrulline malate enhanced aerobic energy production, augmented muscular force output, and mitigated muscle fatigue.

What is Citrulline Malate?

In this regard, citrulline malate (brand name Stimol) was originally developed to improve the muscle performance of patients suffering from asthenia [lack of energy] and to improve recovery time from physical activity for individuals with acute diseases. Citrulline malate is made of L-citrulline and malate. L-citrulline is a nonessential amino acid produced endogenously in the body through 2 key metabolic processes. First, L-citrulline can be synthesized in the intestinal tract from the amino acid glutamine. Also, L-citrulline can be synthesized from the conversion of L-arginine to nitric oxide in a reaction catalyzed by nitric oxide synthase enzymes. Importantly, oral L-citrulline, unlike oral L-arginine, bypasses the hepatic [liver] metabolism and is not catabolized by arginase enzymes, thus allowing it to be transported to the kidneys where approximately 80% of L-citrulline is converted into plasma arginine by the cells of the proximal tubules. The beneficial effects of citrulline malate may actually be attributed to the synergistic combination of both L-citrulline and malate at the muscles’ metabolic level. In particular, increased rates of adenosine triphosphate (ATP) during exercise, followed by an increased rate of phosphocreatine recovery after exercise have been observed.

Research on Citrulline Malate

Perez-Guisado and Jakeman (2010) investigated the effects of a single dose of citrulline malate (8 g) on repeated bouts of upper-body resistance exercise performance. The authors also measured muscle soreness 24 and 48 hours after the high-intensity session. The authors reported that citrulline malate supplementation increased the work performed (repetitions) during an upper-body resistance exercise protocol and mitigated muscle soreness at 24 and 48 hours after exercise in comparison with the placebo (PL) treatment.

Wax (2015) designed a randomized, counterbalanced, and double-blind experiment. Subjects reported to the laboratory 3 times (i.e., session 1, session 2, and session 3) at the same time of day. Session 1 was used to obtain anthropometric data and obtain the 1 repetition maximum (1RM) for each subject in each of the 3 exercises (i.e., leg press, hack squat, and leg extension). During session 2, half of the subjects chosen at random ingested a citrulline malate solution (described below) and the other half consumed a PL solution 60 minutes before the exercise protocol (described below). On session 3, subjects were crossed over and consumed the other supplement and then performed the same exercise protocol. There was a 7-day period between sessions 1 and 2 and between sessions 2 and 3. Subjects in the citrulline malate group ingested 8 g of over-the-counter pharmaceutical grade citrulline malate. Both the placebo and citrulline malate were mixed with crystal light.

How Citrulline Malate Works

The citrulline malate trial experienced less fatigue to the working muscles compared with the PL group, allowing them to perform more repetitions, particularly on rounds 4 and 5. Furthermore, the data showed that blood lactate, heart rate, and blood pressure are not alterer after either citrulline malate or PL supplementation.

The precise mechanism by which citrulline malate enhances exercise performance remains elusive; however, several have been proposed:

  1. Malate is an intermediate of the TCA and increased levels through supplementation may augment energy production by allowing malate to act as a shuttle between the sarcoplasma and mitochondria, thus mitigating the formation of lactic acid, increasing pyruvate genesis, and enabling the glycolytic process.
  2. Increased production of nitric oxide, which regulates functions of the mammalian muscle, including contractile functions, nutrient delivery, and muscle fiber repair, through satellite cell activation and myotrophic factors.
  3. Alterations in acid base balance.

Although citrulline malate supplements are marketed to improve muscle performance through a reduction in lactic acid and ammonia production, this doesn’t seem to be the case.  Improved muscle performance occurring during the strength protocol, blood lactate remained indifferent comparing the citrulline malate treatment to the PL treatment.  The known capacity of citrulline malate to increase plasma L-arginine and act as a buffer to lactate and hyperammonemia remains valid.


  1. Perez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 24: 1215–1222, 2010.
  2. Wax B, Kavazis AN, Weldon K, Sperlak J.Effects of supplemental citrulline malate ingestion duringrepeated bouts of lower-body exercise in advancedweightlifters. J Strength Cond Res. 2015 Mar;29(3):786-92. doi: 10.1519/JSC.0000000000000670.

Written by John Mullen

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