After protein powder and creatine, pre-workout supplements are arguably the most popular category of dietary supplements. Pre-workout supplements are a broad range of products that can include a variety of natural ingredients, including creatine and amino acids.
Two of the most common ingredients used in pre-workout dietary supplements are the nonessential amino acids L-citrulline and L-arginine. Citrulline and L-arginine are amino acids responsible for nitric oxide production, which helps improve blood flow.
Nitric oxide boosters are the most common and effective pre-workout supplements, so citrulline and L-arginine are the perfect ingredients. In this article, we will dive into research to compare L-arginine vs. L-citrulline to help you determine which amino acid is the best for dietary supplements.
Table of Contents:
What Is L Citrulline?
What Is L Arginine?
L Arginine & L Citrulline: What’s The Relationship?
What Are The Benefits Of L Arginine & Citrulline Supplements?
Side Effects
How Much L-Arginine And L-Citrulline Should I Take?
Can You Take L-Arginine And L-Citrulline Together?
Which Is Better, L-Arginine Or L-Citrulline?
FAQs
What is L citrulline?
L-citrulline is an amino acid that exists naturally in the body and is obtained through certain foods. Citrulline is a non essential amino acid since it is produced in the body during the urea cycle. L-citrulline is a known as a precursor to the amino acid L-arginine, which also plays a crucial role in the urea cycle.
The urea cycle is the process in the liver that converts the highly toxic chemical ammonia into urea (urine) to remove waste from the body. Aside from the urea cycle, L-citrulline also plays a significant role in nitric oxide synthesis. Nitric oxide is important because it helps blood vessels relax and widen, which improves blood flow and circulation. This causes blood pressure levels to drop, which helps improve athletic performance and leads to several other benefits, which we will explore below.
L-citrulline has a wide range of uses in the dietary supplementation world. Its most common use is by athletes and gym-goers to increase endurance and reduce fatigue to improve performance. It is commonly used in pre-workout supplements to increase nitric oxide production, which helps enhance “the pump.”
Citrulline supplements are available in various forms, but it is most commonly in powder or capsule form. Citrulline supplements come in two forms:
L-Citrulline: Regular citrulline amino acid.
Citrulline Malate: Citrulline combined with malic acid (malate). Malate is vital for ATP production, which is the body’s energy source. Most pre-workout and sports supplements use citrulline malate to provide extra energy.
It can also be found in certain foods, with watermelon containing the highest amount, particularly in the white rind near the skin. Other foods that contain citrulline include squash, pumpkins, melons, nuts, legumes, and many protein-rich foods such as poultry, beef, and pork.
What is L Arginine?
L-arginine is one of twenty amino acids that are the building blocks of all the body’s proteins. There are nine essential amino acids that the body does not produce naturally and, therefore, need to be obtained through food and dietary supplements.
L-arginine is considered a semi-essential amino acid or conditionally essential because healthy subjects can typically produce it under regular conditions, but there are situations, like when you’re sick or stressed, when the body can’t produce it. If you’re ever concerned about not producing enough amino acids, ask your doctor about a plasma amino acids test.
Like L-citrulline, arginine plays a significant role in nitric oxide production. Once the body obtains arginine, a family of enzymes called nitric oxide synthase (NOS) converts the arginine into nitric oxide and L-citrulline. The nitric oxide relaxes, or widens, the blood vessels, leading to several health benefits. Besides nitric oxide production, arginine can follow the arginase pathway, which is when arginine is broken down into urea for the urea cycle.
Arginine can be obtained in many high protein low fat foods, such as chicken, seafood, soy, whole grains, and dairy products. Arginine supplements come in various forms including liquid, powder, and capsules. It is used similarly to citrulline, particularly as a pre-workout supplement to promote nitric oxide synthesis.
L Arginine vs L Citrulline: What’s The Relationship?
L-arginine and citrulline have a cyclical relationship with each other and the amino acid ornithine. The primary connection between l citrulline and arginine starts with the urea cycle. When amino acids break down, they release ammonia, which is highly toxic to the body. This process removes toxic ammonia from the body by converting it into urea, which then is excreted in urine.
Arginine degradation results in the production of the amino acid ornithine. Ornithine removes ammonia and detoxes the blood in a reaction that produces citrulline. The citrulline is then converted into arginine in the kidneys, then broken down into urea and excreted as urine. During this process, the arginine also releases ornithine, which causes the cycle to start over. The process of breaking arginine down into urea and ornithine is called the arginase pathway.
Arginine can also follow the nitric oxide synthase pathway, which is the process for nitric oxide production. During this process, nitric oxide synthase catalyzes arginine into nitric oxide and citrulline. This process demonstrates how arginine can be converted into citrulline, and citrulline can be converted into arginine during the urea cycle.
To summarize, citrulline is formed from the amino acid ornithine at the start of the urea cycle. Citrulline then converts into arginine, which helps produce urea that is excreted in urine. During arginine’s conversion to urea, it also releases ornithine, triggering the cycle again. Conversely, the nitric oxide synthase pathway can convert arginine into citrulline.
What Are The Benefits Of L Arginine Supplements?
As you will notice, the majority of benefits from L-arginine come from its ability to increase nitric oxide production. Below are some of the top benefits of L-arginine supplements:
1) Increase exercise performance:
One of the primary reasons that people use L-arginine is to improve performance during high intensity exercise. L-arginine promotes nitric oxide production, which helps improve muscle blood flow.
Studies show that improved blood flow can help deliver nutrients quicker and remove waste from the muscles, increasing muscular endurance and reducing fatigue. A systematic review of 18 studies concluded that arginine supplementation significantly improved aerobic or anaerobic performance1.
2) Improve cardiovascular health:
Another benefit of arginine related to the production of nitric acid is improved cardiovascular health. Nitric acid causes blood vessels to relax, improving blood flow.
In this case, the increase in blood flow helps improve circulation and lower blood pressure. Studies show arginine supplementation can help in the treatment of various cardiovascular disorders and hypertension2.
3) Treat Erectile Dysfunction:
One of the benefits of both L arginine and citrulline is that it can improve erectile dysfunction.
A review of ten trials showed oral arginine led to significant improvements in erectile function, overall satisfaction, and orgasmic function compared to the placebo group. They concluded that arginine can effectively treat mild to moderate erectile dysfunction3.
4) May increase testosterone:
Studies have shown that arginine can increase testosterone in animals; however, it does not in humans directly. Although arginine does not directly increase testosterone, it can indirectly stimulate testosterone production by improving blood flow and increasing nitric oxide production.
To learn more about the relationship between L arginine and testosterone, check out our article: Does L Arginine Increase Testosterone?
5) Improve Immune function:
Arginine has an effect on various parts of the body, including the immune system. Research suggests that L-arginine can help improve immune function and prevent disease.
What Are The Benefits Of Citrulline Supplements?
Citrulline supplementation has nearly identical benefits to arginine, which makes sense, considering they are similar. The benefits of citrulline slightly outweigh those of arginine because it is more efficient at nitric oxide production. Benefits of citrulline supplementation include:
1) Increase exercise performance:
A review of eight studies found that six to eight grams of citrulline supplementation 40-60 minutes before physical performance led to increases in repetitions compared to a placebo.
They concluded that citrulline supplementation can delay fatigue and enhance muscle endurance during high intensity exercise4
2) Reduce muscle soreness:
Another benefit of citrulline that is beneficial to athletes is its ability to help reduce muscle soreness and support muscle recovery. A systematic review analyzed the effect that citrulline supplementation has on more soreness and blood lactate levels post-exercise.
They found that consuming three to four grams of L-citrulline, or 8 grams of citrulline malate, one hour before exercise led to a significantly lower rating of perceived exertion and muscle soreness 24- and 48-hours post-exercise5.
3) Improve cardiometabolic health:
Like arginine, citrulline also helps improve cardiovascular health and related disorders. Diminished levels of nitric acid can lead to several age- and lifestyle-related diseases, including high blood pressure, type 2 diabetes, insulin resistance, and cardiovascular disease.
Studies show that a minimum effective dose of 3 grams of L-citrulline up to the maximum effective dose of 10 grams daily can help reduce the risk of such cardiometabolic disorders by increasing nitric oxide levels6.
4) Treat Erectile Dysfunction:
Also, like arginine, citrulline can be used as a natural way to treat erectile dysfunction. One study examined the effects that 1.5 grams daily of oral L-citrulline supplementation had on improving symptoms of erectile dysfunction.
The results showed significant improvements in erection hardness and treatment satisfaction with oral L-citrulline7.
5) Improve insulin sensitivity:
One study examined the effects of citrulline supplementation on improving insulin sensitivity in rats. The results showed that consuming L-citrulline daily for eight weeks improved insulin resistance associated with enhanced insulin sensitivity.
There is a need for more comprehensive research in humans, but the results are promising8.
Arginine vs Citrulline: Side Effects
Most people do not experience side effects with arginine or citrulline, and if they do, they are usually mild. The most common side effects are gastrointestinal distress. To avoid side effects, avoid consuming more than 9 grams daily of L-arginine or 8 grams of L-citrulline.
Possible side effects:
Bloating
Stomach discomfort
Diarrhea
Abdominal pain
Nausea
Headaches
Allergic reaction
Gout
Both amino acids can interact with certain medications or conditions. Some medications and people that should avoid taking arginine and citrulline include:
People with low blood pressure
Erectile dysfunction medication
Nitrates
Blood thinners
Gastroesophageal reflux disease (GERD) or acid reflux
Diuretics
Diabetes medication
How Much L-arginine And L-citrulline Should I Take?
The dosage of L-arginine or L-citrulline will depend on your reason for taking it and your desired goals. A general rule of thumb is that arginine will have twice the dosage as citrulline since citrulline is roughly twice as potent.
For every 1.75 grams of citrulline malate, there is 1.0 gram of citrulline and 0.75 grams of malate. Therefore, the dosage for citrulline malate is nearly double that of L-citrulline.
Purpose
Supplement
Dosage
Overall Health
L-Arginine
2-6 grams daily
L-Citrulline
1-3 grams daily
Citrulline Malate
8 grams daily
Improved Athletic Performance
L-Arginine
5-9 grams 40-60 minutes before exercise
L-Citrulline
2-6 grams 40-60 minutes before exercise
Citrulline Malate
6-8 grams 40-60 minutes before exercise
Erectile Dysfunction
L-Arginine
1.5-5 grams daily
L-Citrulline
3 grams (one gram taken three times daily)
Blood Pressure
L-Arginine
6-10+ grams daily
L-Citrulline
3-6 grams daily
Can You Take L Arginine And L Citrulline Together?
Yes, ideally, arginine and l citrulline should be taken together. However, if you only want to pick one to start with, you would be better off choosing L-citrulline. But, keep in mind, research shows that arginine and citrulline have a synergistic effect, working together to increase plasma concentrations of nitric oxide far greater than they can individually.
A study using rats and New Zealand white rabbits compared oral arginine supplementation, citrulline supplementation, and a combination of both. The results showed that taking citrulline and arginine together caused a more rapid increase in plasma arginine concentration and enhanced nitric oxide metabolism9.
Considering they work significantly better when used together, it would be best to take both, preferably in one product. It is also far more cost-efficient to purchase a combination product that contains both arginine and citrulline rather than the individual amino acids.
For example, a bottle of Nutricost L-Arginine is comparable to a bottle of Nutricost L-Arginine + L-Citrulline. You don’t pay more for the product that has both in it.
Citrulline vs Arginine: Which Is Better?
As I briefly mentioned above, L-citrulline is slightly better than L-arginine because it produces more nitric oxide and increases arginine availability. One study compared L-citrulline and L-arginine for their efficiency in increasing arginine availability in mice. The results showed that citrulline supplementation led to a higher plasma arginine concentration than arginine.
Arginine increased plasma arginine concentration from 109 mol/L to 159, whereas citrulline increased plasma arginine concentration from 109 mol/L to 21410. Other research confirms that citrulline is roughly twice as potent as arginine when it comes to increasing plasma concentration11.
Ideally, you should take a product with both arginine and citrulline to maximize benefits, but if you have to choose between the two, pick L-citrulline. The majority of the most well-known pre-workout products contain citrulline malate. The best L-citrulline supplement is Cellucor C4. C4 is a combination of citrulline malate, creatine, caffeine, and CarnoSyn Beta-alanine, designed to improve your energy, endurance, and focus.
C4 Original is built to take your energy, muscular endurance, and pumps to the next level. Ranging from beginners all the way up to the elite competitors, C4 pre-workout products ignite…
The best L-arginine supplement available is NOW Supplements L-Arginine. Each serving contains 1 gram of high-quality L-arginine from a highly reputable supplement manufacturer.
FAQs
In this section, we will answer some of the most common questions related to L-arginine vs. L-citrulline.
Does L-citrulline increase testosterone?
Citrulline does not directly increase testosterone. However, it may indirectly help increase testosterone. If you’re interested in increasing your T-levels, check out our article: How To Boost Testosterone Naturally.
What should I not mix with L-arginine?
Certain medications do not mix with L-arginine, including blood pressure medications, blood thinners, nitroglycerine, and diuretics.
Is it OK to take L-citrulline every day?
Yes, it is recommended to take L-citrulline every day to maximize health benefits. Make sure to start at the lowest effective dosage.
Do you need to cycle L-arginine?
Yes, L-arginine should be cycled every two months by taking two months off. You can repeat the cycle if you take time off in between.
Is citrulline better than creatine?
Citrulline may be better than creatine for pre-workout because it increases nitric oxide and increases blood flow, which can help get a better pump. However, creatine is better for building strength and mass.
How fast does l-arginine work?
It takes roughly thirty to sixty minutes for L-arginine to work, which is why people use it about an hour prior to exercise.
Does citrulline burn fat?
Citrulline can help burn fat indirectly. It increases exercise performance, which allows people to have more efficient workouts. Citrulline also can help improve insulin sensitivity, which is vital for maintaining blood sugar control and burning fat.
Why do bodybuilders use L-arginine?
L-arginine provides several key benefits to bodybuilders, including increased nitric oxide production, improved performance, reduced soreness, and it may help increase testosterone indirectly.
L Arginine vs l citrulline: Final Takeaways
When comparing l-citrulline vs. l-arginine, you will notice several similarities because the amino acids are so closely related. L-citrulline is a precursor to L-arginine because it converts during the urea cycle to help the body remove waste. Conversely, arginine can follow the nitric oxide synthase pathway, which is the process of nitric oxide production.
During this process, nitric oxide synthase catalyzes arginine into nitric oxide and citrulline. These two processes are vital for maintaining overall health and increasing nitric oxide, which is beneficial for athletic performance. Studies have shown that citrulline supplementation is more efficient at increasing plasma arginine concentration than arginine itself. Citrulline is roughly twice as potent as arginine, which is why citrulline is more commonly used for exercise and found in pre-workout supplements.
Studies have shown a synergistic effect with L-arginine and L-citrulline, as combining both is better than each amino acid. Ideally, you should choose a product that contains both to maximize nitric oxide production and increase blood flow. However, if you have to choose between the two, L-citrulline is the better supplement for improving performance. Pre-workout products typically use citrulline malate for an added energy boost, so be sure to pay attention to the dosages.
To learn about the best supplements containing l arginine and l citrulline, check out our articles: 7 Best Nitric Oxide Supplements To Pump You Up and 7 Best Pump Pre-Workout Supplements!
References:
Viribay, Aitor, et al. “Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis.” Nutrients, vol. 12, no. 5, 2 May 2020, p. 1300, https://doi.org/10.3390/nu12051300.
Sudar-Milovanovic, Emina, et al. “Benefits of L-Arginine on Cardiovascular System.” Mini-Reviews in Medicinal Chemistry, vol. 16, no. 2, 11 Nov. 2015, pp. 94–103, https://doi.org/10.2174/1389557515666151016125826.
Rhim, Hye Chang, et al. “The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis.” The Journal of Sexual Medicine, vol. 16, no. 2, 1 Feb. 2019, pp. 223–234, pubmed.ncbi.nlm.nih.gov/30770070/, https://doi.org/10.1016/j.jsxm.2018.12.002.
Vårvik, Fredrik Tonstad, et al. “Acute Effect of Citrulline Malate on Repetition Performance during Strength Training: A Systematic Review and Meta-Analysis.” International Journal of Sport Nutrition and Exercise Metabolism, vol. 31, no. 4, 2021, pp. 1–9, https://doi.org/10.1123/ijsnem.2020-0295.
Rhim, Hye Chang, et al. “Effect of Citrulline on Post-Exercise Rating of Perceived Exertion, Muscle Soreness, and Blood Lactate Levels: A Systematic Review and Meta-Analysis.” Journal of Sport and Health Science, Feb. 2020, https://doi.org/10.1016/j.jshs.2020.02.003.
Allerton, Timothy D., et al. “L-Citrulline Supplementation: Impact on Cardiometabolic Health.” Nutrients, vol. 10, no. 7, 1 July 2018, p. 921, www.mdpi.com/2072-6643/10/7/921/htm, https://doi.org/10.3390/nu10070921.
Cormio, Luigi, et al. “Oral L-Citrulline Supplementation Improves Erection Hardness in Men with Mild Erectile Dysfunction.” Urology, vol. 77, no. 1, Jan. 2011, pp. 119–122, https://doi.org/10.1016/j.urology.2010.08.028.
Hisae Yoshitomi, et al. “L-Citrulline Increases Hepatic Sensitivity to Insulin by Reducing the Phosphorylation of Serine 1101 in Insulin Receptor Substrate-1.” BMC Complementary and Alternative Medicine, vol. 15, no. 1, 18 June 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4472399/, https://doi.org/10.1186/s12906-015-0706-4.
Morita, Masahiko, et al. “Oral Supplementation with a Combination of L-Citrulline and L-Arginine Rapidly Increases Plasma L-Arginine Concentration and Enhances NO Bioavailability.” Biochemical and Biophysical Research Communications, vol. 454, no. 1, Nov. 2014, pp. 53–57, https://doi.org/10.1016/j.bbrc.2014.10.029.
Agarwal, Umang, et al. “Supplemental Citrulline Is More Efficient than Arginine in Increasing Systemic Arginine Availability in Mice123.” The Journal of Nutrition, vol. 147, no. 4, 1 Apr. 2017, pp. 596–602, www.ncbi.nlm.nih.gov/pmc/articles/PMC5368575/, https://doi.org/10.3945/jn.116.240382.
Khalaf, David, et al. “The Effects of Oral L-Arginine and L-Citrulline Supplementation on Blood Pressure.” Nutrients, vol. 11, no. 7, 22 July 2019, p. 1679, https://doi.org/10.3390/nu11071679.
Van de Poll MCG, Siroen MPC, van Leeuwen PAM, Soeters PB, Melis GC, Boelens PG, Deutz NEP, Dejong CHC. Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am J Clin Nutr, 2007; 85 :167–72.
