L-Arganine vs L-Citrulline: Which Is Better?

Protein powders and creatine might get all the limelight, but pre-workout supplements are climbing the ranks in the fitness world. These supplements are a mixed bag, with everything from the familiar creatine to a range of amino acids thrown into the mix.

Among the stars of the pre-workout scene are the amino acids L-citrulline and L-arginine. They’ve got a special role in pumping up nitric oxide levels in the body, which is great for keeping the blood flowing when you’re pushing through those workouts.

When it comes to pre-workout boosters that get your blood racing, nitric oxide enhancers are where it’s at. That’s why L-citrulline and L-arginine are so often the go-to. We’re going to delve into the science and hash out the details on L-arginine versus L-citrulline, to figure out which one really gives your pre-workout that extra edge.

What is L-Citrulline?

L-citrulline is an amino acid that’s made by the body and also found in some foods. It’s not considered essential because our bodies are equipped to produce it naturally. One of its key roles is serving as a precursor to L-arginine, another amino acid, within the urea cycle.

The urea cycle is essential for detoxifying ammonia in the liver, turning this harmful substance into urea, which is then eliminated from the body. Beyond its role in detoxification, L-citrulline is also pivotal in the production of nitric oxide, a compound that relaxes blood vessels for better circulation and reduced blood pressure. These effects are especially appreciated by athletes and those engaging in rigorous physical activity, as they can enhance performance and reduce fatigue.

When it comes to supplementation, L-citrulline is commonly found in two forms: the standard amino acid and citrulline malate, which is mixed with malic acid to assist in energy production. This supplement is a staple in pre-workout regimens for its role in boosting nitric oxide levels, leading to improved muscle endurance and ‘the pump. While available in powder and capsule forms, citrulline is also naturally present in certain foods like watermelon, particularly the white rind close to the skin, and in other items such as squash, nuts, and meats.

 

What is L-Arginine?

Shifting focus to L-arginine, it’s one of the twenty amino acids that are foundational for protein construction in the body. While nine essential amino acids can’t be produced by the body and must be ingested, L-arginine stands out as semi-essential or conditionally essential. Typically, the body can synthesize enough on its own, but during times of illness or stress, supplementation might be necessary.

L-arginine also contributes to nitric oxide production. In the body, enzymes convert it into nitric oxide and L-citrulline, aiding in vascular relaxation. Besides this, arginine can be metabolized into urea through the arginase pathway, part of the urea cycle.

Rich in proteins and low in fat, foods like chicken, seafood, soy, and grains are good sources of arginine. It’s available as a supplement in liquid, powder, or capsule form, and like citrulline, is popular among athletes for its nitric oxide-boosting properties.

Examining the connection between L-arginine and L-citrulline, they’re linked through the urea cycle and nitric oxide production. The cycle starts with the conversion of ammonia to urea, with arginine breaking down into ornithine and then into citrulline, which can be converted back into arginine. This interplay exemplifies the cyclical relationship between these amino acids. Arginine is also a precursor to citrulline through the nitric oxide synthase pathway, illustrating their mutual conversion possibilities within the urea cycle and beyond.

 

Relationship Between L-Arginine and LCitrilline

L-arginine and L-citrulline share a dynamic relationship, intricately linked by the urea cycle and their mutual transformation into each other. This cycle is crucial for eliminating the toxic byproduct ammonia that results from amino acid breakdown. Within this cycle, L-arginine breaks down into ornithine, which then combines with ammonia to detoxify it, producing citrulline in the process. Citrulline is transported to the kidneys, where it’s transformed back into arginine, completing the cycle as it’s further metabolized into urea for excretion.

This isn’t the only path these amino acids travel. L-arginine is also involved in producing nitric oxide, a vital compound for cardiovascular health. Enzymes within the body work to convert L-arginine into nitric oxide and L-citrulline. This not only serves the cardiovascular system but also loops citrulline back into the urea cycle, ready to be changed into arginine again.

To encapsulate their connection, citrulline originates from ornithine at the onset of the urea cycle, transitioning into arginine, which then aids in generating urea for disposal. Simultaneously, arginine contributes to nitric oxide production, which, in turn, generates more citrulline, perpetuating this essential biological dance.

 

The Benefits of L-Arginine Supplements

The advantages of L-arginine supplements are largely tied to their capacity to boost nitric oxide levels. Here’s how they can impact your health and performance:

1. Enhanced Exercise Performance:
   L-arginine is popular among those looking to enhance their workout. By increasing nitric oxide, it improves blood flow to muscles, potentially increasing nutrient delivery and waste removal, which may improve endurance and lessen fatigue. Research supports its role in boosting both aerobic and anaerobic activities.(1)
2. Cardiovascular Health:
   The cardiovascular system also benefits from L-arginine’s ability to produce nitric oxide, which helps relax blood vessels and improve circulation. Studies indicate that it can aid in managing cardiovascular diseases and hypertension.(2)
3. Erectile Dysfunction Treatment:
   Both L-arginine and citrulline have been shown to aid in the treatment of erectile dysfunction. Clinical trials have found significant improvements in erectile function with arginine supplementation when compared to a placebo.(3)
4. Testosterone Levels:
   While arginine doesn’t directly increase testosterone in humans, it may indirectly promote its production by enhancing blood flow and nitric oxide levels.
5. Immune System Boost:
   L-arginine has beneficial effects on the immune system. Studies suggest it can enhance immune responses and disease prevention.

The Benefits of Citrulline Supplements

Citrulline offers similar benefits to arginine but is more effective in nitric oxide production, which can lead to even more pronounced benefits:

1. Exercise Performance Boost:
   Citrulline supplementation has been linked to increased endurance and delayed fatigue in high-intensity exercise, with studies showing improved performance.(4)
2. Muscle Soreness Reduction:
   It may also help in reducing muscle soreness and aiding recovery, with evidence supporting its use in decreasing perceived exertion and muscle soreness post-exercise.(5)
3. Cardiometabolic Health:
   Citrulline also contributes to cardiovascular health and may prevent related diseases. Regular supplementation could lower the risk of high blood pressure, type 2 diabetes, and other cardiometabolic disorders by boosting nitric oxide.(6)
4. Erectile Dysfunction:
   Similar to arginine, citrulline may also treat erectile dysfunction naturally. Studies show that L-citrulline supplementation has led to notable improvements in erectile hardness and satisfaction.(7)
5. Insulin Sensitivity:
   In animal studies, citrulline has been shown to improve insulin sensitivity and resistance, with promising, yet preliminary, results that need further exploration in human research.(8)

Side Effects of Arginine vs Citrulline

While side effects from arginine or citrulline are rare and generally mild, they can occur, predominantly as gastrointestinal issues. To minimize potential side effects, it’s advisable not to exceed a daily intake of 9 grams of L-arginine or 8 grams of L-citrulline.

Some possible side effects include:

• Bloating
• Stomach discomfort
• Diarrhea
• Abdominal pain
• Nausea
• Headaches
• Allergic reactions
• Gout

Certain individuals and those on specific medications should exercise caution with these supplements:

• Individuals with low blood pressure
• Those taking erectile dysfunction medications, nitrates, or blood thinners
• People with GERD or acid reflux
• Those on diuretics or diabetes medications

 

Optimal Dosages of L-Arginine and L-Citrulline

The ideal dosage depends on your health goals and the reasons for supplementation. Since citrulline is more potent, the dosage is generally lower than that of arginine.

• For general health, 2-6 grams of L-Arginine or 1-3 grams of L-Citrulline daily.
• For enhanced athletic performance, 5-9 grams of L-Arginine or 2-6 grams of L-Citrulline before exercise.
• For erectile dysfunction, 1.5-5 grams of L-Arginine or 3 grams of L-Citrulline spread throughout the day.
• For blood pressure concerns, 6-10+ grams of L-Arginine or 3-6 grams of L-Citrulline daily.

 

Combining L-Arginine and L-Citrulline

Taking arginine and citrulline together is often recommended for their synergistic effects, which can significantly boost nitric oxide levels. Studies have shown that the combination increases plasma arginine concentration and enhances nitric oxide production more effectively than either amino acid alone.

 

Citrulline vs Arginine: Which is Superior?

L-citrulline edges out L-arginine in efficacy by yielding more nitric oxide and raising arginine levels more effectively. Research has demonstrated that citrulline supplementation results in a higher plasma arginine concentration compared to taking arginine directly. Thus, while both can be taken together for maximum benefit, L-citrulline alone may be the better choice, particularly as it is a common ingredient in many pre-workout supplements. For example, Cellucor’s C4 pre-workout blend combines citrulline malate with other ingredients to enhance energy, endurance, and focus during exercise.

 

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.