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Is Citrulline the New Arginine?

As discussed in our Citrulline article, citrulline supplementation leads to a greater increase in blood arginine that arginine itself. The next logical question is whether citrulline supplementation can increase nitric oxide levels. This was proven in a study published in 2009, where pre-professional cyclists were given 6 grams of citrulline prior to a 4-hour race3. Following this study, there has been a flurry of studies examining citrulline’s effect on a range of exercise performance parameters. Most of these studies have used a form of L-citrulline called L-citrulline-malate. Complexing malate with citrulline is thought to provide additional ergogenic benefits. These are thought to be mediated through a number of key mechanisms1 which will be discussed below. Lastly, this article will detail the exciting findings from a study on citrulline and strength training.

Citrulline-Malate Decreases Ammonia

Citrulline is a component of the body’s urea cycle, which is responsible for converting ammonia to urea. Ammonia is a toxic product of exercise that inhibits muscle contraction when exercising at high intensities such as in the gym when doing any type of set with greater than 6-7 reps.

Citrulline-Malate Decreases Lactate Levels

Malate is a key component of the Kreb’s cycle, which is the body’s main metabolic pathway for extracting energy from carbohydrates, fat and protein. Providing additional malate is thought to drive the Kreb’s cycle, which helps decrease lactate production. Malate also has an indirect role in decreasing ammonia levels.

Citrulline-Malate Increases Nitric Oxide Levels

NO regulates many functions of skeletal muscle including glucose uptake, fat oxidation, contractile functions, blood flow and repair. Increasing NO levels is thought to have a beneficial effect on these functions.

Citrulline Benefits Multiple Types of Exercise

As highlighted briefly above, there have been numerous studies on L-citrulline-malate, which have measured its effect on a range of different exercise and muscle performance parameters. Recently, two studies conducted by the same research group showed an increase in plasma NO metabolites in well trained endurance athletes after a cycling competition; these athletes were supplemented with only one dose of L-citrulline-malate (6 g) 2 hours before exercise2, 3. Two studies using rat models have found supplementation with L-citrulline-malate to improve the efficiency of muscle contraction4, 5. Lastly, a study of men complaining of fatigue found that L-citrulline-malate improved muscle energetics by promoting aerobic function6. So the science is pretty solid when it comes to L-citrulline-malate’s positive effect on exercise performance. What’s not clear is the exact mechanism by which L-citrulline-malate exerts its effects. It’s most likely to be a combination of factors mentioned above7.

Citrulline-Malate Improves Strength Training

There is one more important study worth highlighting that is particularly relevant to individuals looking to use L-citrulline-malate to increase the intensity of their resistance training program. The study was published in 2010 in the Journal of Strength and Conditioning Research and used repeated sets of bench press exercises to muscular failure to test L-citrulline-malate’s capacity to improve anaerobic performance. The study was of the highest scientific standard possible; it involved 41 male subjects and used a randomized, double-blind, 2-period crossover design. For the unacquainted, this type of study design is considered the ‘gold standard’ in science.

Strength Training Program Used to Test L-Cirtulline-Malate

In each session, subjects completed a total of 16 sets of exercises. The first 4 sets consisted of the flat barbell bench press exercise at 80% of 1RM until repetition failure, with each set separated by 1-minutes rest. The next 4 sets consisted of the incline barbell bench press exercise to muscular failure using the same weight and rest period as the first exercise (i.e. flat barbell bench press). The next 4 sets consisted of the incline dumbbell flyes exercise at 60% of 1RM for the flat barbell bench press. The last 4 sets were a repeat of the first four, namely, flat barbell bench press exercise at 80% of 1RM to muscular failure. Each time, the researchers recorded the number of repetitions conducted in the 8 sets of flat barbell bench presses (i.e. 4 at the start and 4 at the end). A layout of the sequence of each session from the study is provided below.

L-Citrulline-Malate Increases Strength and Reduces Muscle Soreness

In what can be considered very encouraging findings; the number of repetitions showed a significant increase from placebo treatment to L-citrulline-malate treatment. By the time participants reached the last set, there was an average increase of 52.92% in repetitions, with every participant showing a positive response! What’s more, participants reported an average decrease of 40% in muscle soreness at 24 hours and 48 hours after the pectoral training session when supplementing with L-citrulline-malate prior to the workout. For those that like the nitty gritty info, the detailed findings from the study are summarised in the table below.

Timing & Dose of L-Citrulline-Malate

Some important points to highlight from the study are the timing and amount of L-citrulline-malate used. Each subject received 8 grams of L-citrulline-malate 1-hr prior to their workout. If you want to replicate this dosing regime by using L-citrulline-malate-containing supplements from; it’s important to check the label carefully. Many pre-workout supplements only contain 1-2 grams of citrulline, while for others it’s impossible to know because L-citrulline-malate is part of a proprietary blend/complex. Whatever the case, it’s likely that you will need to take multiple doses to experience similar effects to those reported in this study.

Training History & Program for L-Citrulline-Malate Study Participants

Some other relevant details about the study are listed below.

  1. All subjects had been weight training >3 hours per week for at least the last 6 months.
  2. All subjects undertook a training program consisting of 5 workouts per week (from Monday to Friday) distributed as follows: Monday for chest, Tuesday for back, Wednesday for legs, Thursday for shoulders, and Friday for arms. Saturday and Sunday were resting days. Subjects rested for 48 hours before the testing day (Monday).
  3. The training program was the same during the 2-week study period (the same weight, exercises, sets, and reps).
  4. The length of washout between treatments was 1 week.

L-Citrulline-Malate Benefits

The reason for listing these specific details is that it allows the reader to see that the subjects’ used in this study where much like your average ‘gym junkie’ – so to speak. The problem with lots of studies is that they often use subjects dissimilar to the typical end-user of the product/substance. For example, some studies use subjects that have no history of weight training or that have not been frequenting the gym in recent weeks and months.  What’s more, some studies will subject participants to an irrelevant or unrealistic training protocol.

One example may be testing the effect of an amino acid on strength training and using subjects that are not familiar with weight training and having them partake in only 1 or 2 weight training sessions a week. If you take someone that is unfit and get them to do a couple of gym session a week, you are almost invariably going to see improvements. The design used in this study makes it very relatable to the regular gym goer who is looking for an edge to increase the intensity of their workout.

Big Results from One-Off Use

The other important point to highlight is that the subjects only took one dose prior to their workout. So no ‘loading’ regime was used, which is often the case with pre-workout supplements. A single dose of L-citrulline-malate once a week might be ideal if you have one day each week where you really like to hit the gym hard. Based on the findings of the aforementioned study, taking L-citrulline-malate may also help reduce muscle soreness in the two days following your intense workout.

L-Citrulline-Malate Supplementation

All-in-all, the findings from the above study are very impressive! It’s worth highlighting the pertinent points, just to emphasize the potential of L-citrulline-malate to improve strength training performance, namely:

  1. Subjects took citrulline-malate as a one-off after completing a 2-week training program very similar to a typical weight training program for a gym enthusiast.
  2. In a single session, this resulted in an increase of almost 53% in reps-to-fatigue in the last set of a session comprising 16 sets.

L-Citrulline-Malate Supplementation is Sound Science

So as a keen bodybuilder or strength training advocate, you can be pretty confident in the science behind L-citrulline-malate. There are multiple animal and human studies showing that it works in a variety of ways to improve exercise performance. But perhaps most important is the study proving L-citrulline-malate’s merit in improving strength and reducing muscle soreness as part of a comprehensive strength training program1. Now who wouldn’t want that?



  1. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research. 2010;24(5):1215-1222.
  2. Sureda A, Cόrdova A, Ferrer MD, et al. L-citrulline-malate influence over branched chain amino acid utilization during exercise. European Journal of Applied Physiology. 2010;110(2):341-351.
  3. Sureda A, Cόrdova A, Ferrer MD, et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radical Research. 2009;43(9):828-835.
  4. Giannesini B, Le Fur Y, Cozzone PJ, et al. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. European Journal of Pharmacology. 2011;667(1-3):100-104.
  5. Giannesini B, Izquierdo M, Le Fur Y, et al. Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat. European Journal of Pharmacology. 2009;602(1):143-147.
  6. Bendahan D, Mattei JP, Ghattas B, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. British Journal of Sports Medicine. 2002;36(4):282-289.
  7. Rau´ l Besco´s, Antoni Sureda, Josep A. Tur. The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012;42(2):99-117.
1-hr prior to their workout
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