Citrulline

What is citrulline?

Citrulline is a naturally occurring alpha-amino acid in the body that is involved in numerous bodily processes. In the field of sports, citrulline is primarily used for an increase in muscle pump and increased blood supply to the trained muscles.

Citrulline is naturally produced by the body and is also found in some foods. By taking citrulline supplements, it is possible to increase citrulline levels in the body beyond normal levels, which is associated with a whole range of health benefits, as well as an increase in athletic performance.

While some people are firmly convinced of the effectiveness of citrulline supplementation in improving overall health and athletic performance, others are more skeptical about this supplement. This article will shed light on the scientific background and show what is really behind this supplement.

Citrulline is an amino acid that was first isolated from watermelons (1). This amino acid is considered non-essential, meaning that the body is capable of producing certain amounts on its own.

Citrulline plays a number of important roles in the body, but unlike other amino acids, citrulline is not used to build body proteins (2). Citrulline is an intermediate in the conversion of the amino acid ornithine to arginine and helps detoxify ammonia during the urea cycle. Ammonia is a harmful waste product of amino acid metabolism that must be disposed of quickly, otherwise it leads to muscle exhaustion and can negatively affect thinking performance. The latter is produced in many metabolic processes, especially in the breakdown of proteins.

Citrulline may also help dilate blood vessels, which improves blood flow to muscles and other body tissue types, and may also play a role in muscle development (3, 4).

How does citrulline work?

Citrulline causes increased nitric oxide production by increasing arginine levels in the body. Interestingly, citrulline is able to increase arginine levels significantly more than orally ingested arginine, which is largely broken down in the liver after ingestion. An increase in nitric oxide production results in a relaxation of the smooth muscle of the walls of the blood vessels, which leads to a widening of the veins and increased blood flow to the body tissues.

Citrulline has a number of important effects in the body. One of the primary mechanisms by which this amino acid exerts its effects is vasodilatation, which has been associated with improved blood flow, lower blood pressure, and increased blood flow (5).

After consumption, some of the citrulline consumed is converted into another amino acid called arginine. Arginine is then converted into a molecule called nitric oxide, which causes veins to dilate by relaxing the muscles in the walls of blood vessels (6). Interestingly, consumption of citrulline can increase arginine levels in the body more than it does after consumption of arginine itself (4). This is related to the different ways in which the body absorbs and processes arginine and citrulline (2). Increases in nitric oxide production and blood flow are among the processes involved in the positive effects of citrulline on exercise performance.

Although citrulline is not an amino acid used directly for building body proteins, it has been shown that citrulline can increase protein synthesis via stimulation of an important signaling pathway involved in muscle building (2, 7). Citrulline can also reduce the uptake of amino acids by the liver, preventing degradation of these amino acids (4).

Because of these dual effects on protein synthesis and amino acid breakdown, citrulline may contribute to the maintenance and building of muscle mass.

• Summary: Citrulline may increase blood flow via an increase in nitric oxide production. It may also have positive effects on muscle building by stimulating protein synthesis and reducing protein breakdown.

Citrulline is naturally found in some widely consumed foods In addition to being produced by the body itself, citrulline is also found in some foods. However, most foods have not yet been studied for their citrulline content.

What are the benefits of increased nitric oxide production from citrulline?

The most noticeable effects of increased nitric oxide production and the resulting improved blood flow to muscle tissue are an increased muscle pump during exercise and a clearly visible improvement in vascularity. Far more interesting, however, is that an increased blood supply to the working muscles results in a better supply of nutrients, oxygen and anabolic hormones to the muscles. This results not only in an increased performance of the muscles, but also in a better and faster regeneration between training sets and after training. In addition to this, better blood flow to the muscles equates to faster removal of toxic metabolic waste products that are produced during intense muscular exertion and can lead to premature muscle fatigue. In combination, all of this means that you can perform more repetitions per training set, more sets per training session, and train more frequently, ultimately resulting in faster gains in muscle mass and strength. What other benefits does citrulline have

Scientific research has shown that citrulline not only improves recovery, but can also reduce muscle soreness after exercise. In addition to this, citrulline increases energy and ATP production and is also the limiting factor for the breakdown of toxic ammonia, which is produced during exercise and can reduce muscle performance.

What are the main benefits of citrulline?

• Strong increase in nitrogen oxide production
• Extreme, literally skin-bursting pump and increased vascularity
• Increased delivery of nutrients, oxygen and anabolic hormones to the trained muscles
• Faster removal of toxic metabolic waste products
• Delayed onset of muscle fatigue
• Faster recovery during and after training
• Increased gains in muscle mass and strength Increased energy/ATP production

Foods known to contain citrulline include (7, 8):

• Watermelon
• Pumpkin
• Cucumber
• Bitter melon

Types of citrulline supplements

There are two primary forms of citrulline used in supplements:

1. L-Citrulline: This is simply citrulline itself without any other attached compounds.
2. Citrulline Malate: This is the combination with a compound called malate, which is important for energy production (9).

Even though both forms have similar effects, citrulline malate is more widely used in sports supplements. However, when citrulline malate is used, it is not clear which effects can be attributed to citrulline and which to malate.

Citrulline has several health benefits

Researchers have considered the potential health benefits of citrulline, which include effects on blood vessels, erectile dysfunction, and athletic performance (5, 10).

Citrulline can help dilate blood vessels

An improved ability to dilate blood vessels can potentially improve blood pressure and blood flow to body tissues. Studies have shown that a single administration of L-citrulline cannot improve the ability of arteries to dilate in healthy and sick people (11, 12).

When people who suffered from heart disease or who were at increased risk for heart disease used L-citrulline for 7 days or longer, an improved ability of the arteries to dilate was observed (13, 14).

Although a single dose may not be effective in terms of dilating the arteries, taking a citrulline supplement can be effective in the long run.

Citrulline can lower blood pressure

Citrulline supplements can lower blood pressure, which seems to be especially true in people with high blood pressure. Studies involving 30 to 40 subjects examined the effects of citrulline supplements in adults with high blood pressure or other cardiovascular problems. These studies concluded that the subjects' blood pressure had decreased by 4 to 15% within 8 weeks (15, 16).

In addition, in a small study of 12 subjects with normal blood pressure, researchers observed that citrulline was able to reduce blood pressure by 6% to 16% after 7 days (17). However, the results in healthy individuals are inconclusive, as other studies have not observed benefits of citrulline over periods of one to four weeks duration (14, 18).

All in all, it remains unclear whether citrulline substantially affects blood pressure in healthy individuals.

Other health benefits of citrulline

Citrulline can enhance the increase in growth hormone levels that can be observed after exercise (19). The increase in levels of growth hormone and other hormones is involved in the body's positive adaptations to exercise (20). Citrulline may also improve erection in men suffering from erectile dysfunction, which is likely due to citrulline's ability to increase blood flow (21).

• Summary: Taking citrulline supplements may lower blood pressure and improve the ability of the arteries to dilate. These effects seem to be more pronounced in people suffering from diseases of the cardiovascular system.

Studies suggest that citrulline may enhance exercise performance

Because of its ability to increase blood flow, citrulline has been studied in the context of endurance and strength training. Several studies that have looked at endurance training have used L-citrulline, while many of the strength training studies have used citrulline malate.

Endurance training

In general, a single dose of citrulline does not appear to improve endurance performance (4). Taking the supplement for one or two weeks did not change oxygen consumption (21). However, citrulline can increase oxygen levels in muscle tissue (22, 23). This means that even though citrulline may not allow the body to use more oxygen bodywide, it could improve oxygen use in exercising muscles. This may ultimately allow for increased exercise performance.

This has been demonstrated in cycling, where exercise performance can be enhanced by taking citrulline supplements. In one study, cyclists who supplemented with citrulline were able to train 12% longer before fatigue set in compared to athletes who used only a placebo (22). The use of citrulline supplements for seven days may also increase strength release during cycling training (21).

All in all, citrulline can positively influence oxygen utilization in the muscle, which can increase endurance.

Strength training

Several studies have shown that citrulline malate can enhance exercise performance when training with weights. One study conducted with 41 men evaluated the effects of citrulline malate on the ability to perform repetitions during upper body exercises. Subjects were able to perform 53% more repetitions after taking citrulline malate than after taking a placebo (24). In addition, muscle soreness was 40% less in subjects during the two days following exercise when they had taken citrulline prior to exercise (25).

Other studies have also found that citrulline malate reduced fatigue and increased lower-body exercise performance (25). In both studies, subjects had taken the supplement 60 minutes before exercise.

• Summary: Citrulline can increase oxygen levels in the muscles and enhance exercise performance. Both endurance performance and performance during a workout with weights can be improved by taking citrulline.

Demand in sport

This amino acid is converted to arginine in the body and can improve nitric oxide (NO) and growth hormone production. Cirtrulline enables longer workouts by delaying the onset of fatigue.

Citrulline is converted relatively quickly in the body in arginine. In this way, more arginine is available for nitric oxide production and the triggering of growth hormone. Citrulline malate is the usual dosage form of this amino acid (citrulline is bound to malate, or malic acid). This combination can also neutralize the lactate (lactic acid) produced during exercise. In this way, the exhaustion during exercise is delayed.

You can take 3g of citrulline (as citrulline malate) twice a day on an empty stomach. On training days, one dosage should be taken 30-60 minutes before training and the second immediately after the end of training.

How much citrulline should one take?

Based on available research, the recommended dosage is 3 to 6 grams of L-citrulline or about 8 grams of citrulline malate. The dosage depends on the dosage form, as 1.75 grams of citrulline malate provides only 1 gram of L-citrulline. The remaining 0.75 grams consist of malate.

There are different recommendations for specific areas of application:

• Training with weights: 8 grams of citrulline malate, which provides approximately 4.5 grams of L-citrulline, appears to be an effective dosage for enhancing exercise performance during training with weights (24, 25).
• Increasing the amount of oxygen in the muscle: To increase the amount of oxygen in the muscle, taking 6 grams of L-citrulline or more per day for at least 7 days in a row seems to be effective (22).
• Lowering blood pressure: To improve blood pressure, the dosage used in the field of scientific research is 3 to 6 grams of L-citrulline.

In addition, unlike other amino acids, dosages greater than 10 grams tend not to cause digestive discomfort (2). Digestive discomfort is a sure way to ruin your workout. Therefore, this is good news if you are using this supplement to boost your workout performance.

Citrulline is probably better tolerated compared to other amino acids due to differences in absorption and processing (2).

• Summary: Dosages of 3 to 6 grams of L-citrulline or 8 grams of citrulline malate appear to be optimal. No side effects have been reported at dosages up to 10 grams.

Citrulline supplements appear to be safe and harmless

Unlike many other supplements, some preliminary information is available on the safety of high dosages of citrulline.

A small study examined different dosages in eight healthy men. Each study participant consumed dosages of 2, 5, 10, and 15 grams of L-citrulline at different times. Even at the highest of the dosages, none of the study participants reported side effects (26).

However, the highest dosage did not seem to increase arginine levels in the blood as much as expected, which means that there seems to be a limit regarding the amount of this supplement above which the body can no longer use it. All in all, this study suggests that dosages above 10 grams are not necessary.

Blood tests taken on the subjects after taking the citrulline supplement did not show any negative changes in normal body functions or blood pressure.

• Summary: Based on current studies, citrulline appears to be safe and well tolerated. However, dosages above 10 grams are probably unnecessary.

Conclusion

Citrulline is an amino acid that has numerous health benefits. It also appears to be safe and harmless, and there are no known side effects so far. This supplement could promote healthier blood vessels and lower blood pressure, which seems to be especially the case for people with heart disease or high blood pressure. Citrulline malate has been studied most extensively in the area of training with weights. Dosages of 8 grams can reduce fatigue and improve exercise performance in the gym.

If you want to boost your heart health or improve your exercise performance, citrulline might be worth a try.

References:

1. https://www.ncbi.nlm.nih.gov/pubmed/16746990
2. https://www.ncbi.nlm.nih.gov/pubmed/23022123
3. https://www.ncbi.nlm.nih.gov/pubmed/27749691
4. https://www.ncbi.nlm.nih.gov/pubmed/25676932
5. https://www.ncbi.nlm.nih.gov/pubmed/22145130
6. https://www.ncbi.nlm.nih.gov/pubmed/25638487
7. https://www.ncbi.nlm.nih.gov/pubmed/24972455
8. https://www.ncbi.nlm.nih.gov/pubmed/23316808
9. https://www.ncbi.nlm.nih.gov/pubmed/16555951
10. https://www.ncbi.nlm.nih.gov/pubmed/17214603
11. https://www.ncbi.nlm.nih.gov/pubmed/26442881
12. https://www.ncbi.nlm.nih.gov/pubmed/24824653
13. https://www.ncbi.nlm.nih.gov/pubmed/26005507
14. https://www.ncbi.nlm.nih.gov/pubmed/21067832
15. https://www.ncbi.nlm.nih.gov/pubmed/21154265
16. https://www.ncbi.nlm.nih.gov/pubmed/26863234
17. https://www.ncbi.nlm.nih.gov/pubmed/27333912
18. https://www.ncbi.nlm.nih.gov/pubmed/19851298
19. https://www.ncbi.nlm.nih.gov/pubmed/20499249
20. https://www.ncbi.nlm.nih.gov/pubmed/23442269
21. https://www.ncbi.nlm.nih.gov/pubmed/21195829
22. https://www.ncbi.nlm.nih.gov/pubmed/26023227
23. https://www.ncbi.nlm.nih.gov/pubmed/27378312
24. https://www.ncbi.nlm.nih.gov/pubmed/20386132
25. https://www.ncbi.nlm.nih.gov/pubmed/25226311
26. https://www.ncbi.nlm.nih.gov/pubmed/17953788

Further reading

1. Bendahan D, Mattei JP, Ghattas B, et al. 2002. citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med; 36(4):282-9.
2. Briand J, Blehaut H, Calvayrac R, Laval-Martin D. 1992. 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):1-22.
3. Callis A, Magnan de Bornier B, Serrano JJ, et al. 1991.Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Drug Research; 41(6):660-3.
4. Fornaris E, Vanuxem J, Duflot P, et al. 1984. [Pharmacological/clinical approach of citrulline malate activity: study of blood lactate levels during standardized muscular exercise]. Gazette Medicale, 91(11):125-128.
5. Goubel F, Vanhoutte C, Allaf O, et al. 1997. citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins. Can J Physiol Pharmacol; 75(3):205-7.
6. Hartman WJ, Torre PM, Prior RL. 1994. dietary citrulline but not ornithine counteracts dietary arginine deficiency in rats by increasing splanchnic release of citrulline. J Nutr; 124(10):1950-60.
7. Janeira MA, Santos PJ. 1998. citrulline malate effects on the aerobic-anaerobic threshold and in post-exercise blood lactate recovery. Med Sci Sports Exerc; 30(5 supp): abstract 881.
8. Vanuxem D, Duflot JC, Prevot H, et al. 1990. [Influence of an anti-astenia agent, citrulline malate, on serum lactate and ammonia kinetics during a maximal exercise test in sedentary subjects]. Sem Hop Paris; 66(9):477-481.
9. Waugh WH, Daeschner CW, Files BA, et al. 2001. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase, two results. J Natl Med Assoc; 93(10):363-71.