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L-Citrulline (Malate) and L-Arginine

·2257 words·11 mins
Rolf Streefkerk MSc
Author
Rolf Streefkerk MSc
IT Entrepreneur and hobbyist fitness and health enthusiast
Table of Contents

Introduction #

L-citrulline and L-arginine are two amino acids that play important roles in various physiological processes, including nitric oxide production, cardiovascular health, and exercise performance. Understanding their sources, health benefits, weight training and endurance benefits, recommended dosages, safety, and special considerations is important for individuals looking to optimize their health and athletic performance. This article will provide a comprehensive overview of these supplements based on, primarily, randomized placebo controlled trials.

What are L-citrulline and L-arginine? #

L-citrulline and L-arginine are naturally occurring amino acids involved in the production of nitric oxide, a molecule that helps to expand blood vessels, improve blood flow, and deliver oxygen and nutrients to various tissues. L-citrulline is found in certain foods like watermelon and some legumes, while L-arginine is found in foods such as red meat, poultry, fish, dairy products, and nuts. Both amino acids can also be taken as dietary supplements, either individually or in combination.

Food sources #

Typically most people will get their L-arginine dosage ranges of 6 to 9 grams per day from food intake. For L-citrulline however, that is a different matter since it’s not readily available in many different types of foods.

L-arginine #

L-arginine is readily available from food, for example per 100 grams:

  1. Soybeans (cooked): 2.1 grams
  2. Meat:
    • Turkey breast (cooked): 2.3 grams
    • Beef (lean, cooked) contains approximately 1.3 to 1.5 grams.
    • Chicken breast (cooked) contains approximately 1.7 grams.
    • Pork loin (cooked) contains approximately 1.4 grams.
  3. Whole eggs: contain approximately 1.1 grams.

L-citrulline #

Watermelon is the most well-known food source of L-citrulline. It contains approximately 250 mg of L-citrulline per 100 grams of watermelon flesh.

There are other food sources that contain trace amounts of L-citrulline, for most people however it means supplementation is the only viable way.

Cardiovascular Health #

Benefits #

In both younger adults as well as the elderly, l-arginine supplementation has shown cardiovascular benefits respectively;

  • Increase nitric oxide production, leading to vasodilation (wider blood vessels) and improved blood flow, which may support cardiovascular health ( 16).
  • and, L-arginine supplementation may help lower blood pressure and reduce the risk of heart disease by increasing nitric oxide production ( 6).

L-citrulline supplementation has also shown benefits to help lower blood pressure and improve overall cardiovascular function ( 1).

Time Efficacy #

  • Immediate effects: L-citrulline 3 grams twice daily, has found increases of NO in the blood after 1 week ( 1).
  • Medium-term effects: Chronic L-arginine supplementation may have positive effects on cardiovascular health, but more research is needed.
  • Long-term effects: Limited evidence is available on the long-term effects of L-arginine supplementation on cardiovascular health.

Suggested Use and Dosage #

L-arginine: A dose of 3-6 grams per day has been used in some studies for cardiovascular health, although its effectiveness remains unclear ( 1, 2).

Safety and Precautions #

L-arginine is generally well-tolerated when taken at recommended dosages for cardiovascular health. People with kidney or liver disease, herpes, or a history of heart attacks should consult their healthcare provider before taking L-arginine supplements ( 17).

Pregnant or breastfeeding women should also consult their healthcare provider before taking L-arginine supplements.

Digestive Health #

Benefits #

There is limited evidence examining the effects of L-citrulline and L-arginine on digestive health, all studies so far that we have found, have been done on rats. Research is clearly more focussed on benefits for endurance and muscle growth and recovery.

Anecdotal Evidence #

There have been anecdotal reports of efficacy for bowel health. See the Now Foods L-Citrulline supplement review.

Energy and Endurance #

Benefits #

L-citrulline Malate supplementation has been shown to improve endurance performance, including increased time to exhaustion and decreased fatigue ( 4).

These findings were nuanced in a critical review of citruline malate studies ( 9), their key findings with respect to exercise performance;

Athletes wishing to explore NO (Nitric Oxide) enhancers are reminded that a good level of evidence exists for L-citrulline to improve exercise performance, and therefore may consider use of this supplement whilst the intricacies of Citrulline Malate supplementation are discovered ( 12).

L-citrulline supplementation has been demonstrated to improve endurance performance, including increased time to exhaustion, decreased fatigue, and improved aerobic energy production ( 3). This may be attributed to its role in promoting nitric oxide production, which can improve oxygen delivery to working muscles and enhance aerobic metabolism. In contrast, L-arginine supplementation alone has not been shown to improve endurance performance consistently.

Time Efficacy #

  • Immediate effects: Acute L-citrulline supplementation has shown improvements in time-to-exhaustion and decreased fatigue during high-intensity exercise after 1-2 hours of ingestion ( 14).
  • Medium-term effects: Chronic L-citrulline supplementation (7 days or more) may further enhance endurance exercise performance ( 3).
  • Long-term effects: Limited evidence is available on the long-term effects of L-citrulline supplementation on endurance.

Suggested Use and Dosage #

L-citrulline: For endurance exercise performance, 6-8 grams of L-citrulline per day, taken 1-2 hours before exercise, has been used in research studies ( 12).

Safety and Precautions #

L-citrulline is generally well-tolerated when taken at recommended dosages for endurance. Mild side effects, such as gastrointestinal discomfort, may occur in some individuals ( 15).

Muscle Growth and Recovery #

Benefits #

There are currently no studies specifically done for L-citrulline (without malate) for Strength training that I’m aware of.

L-citrulline Malate supplementation has been demonstrated to improve resistance exercise performance, such as increased reps and decreased muscle soreness ( 13). The authors noted;

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.

Another study found that L-citrulline Malate can improve resistance exercise performance, including an increased number of reps, improved muscle endurance, and decreased muscle soreness ( 4).

These findings, however, were nuanced in a critical review of L-citrulline Malate studies in 2021 ( 9), their findings regarding strength and recovery;

There is little evidence to advocate its use in the production and maintenance of muscular power, maximal strength, recovery of muscular function, or supporting muscular adaptations currently.

L-arginine supplementation alone has not been consistently shown to improve resistance exercise performance.

Time Efficacy #

  • Immediate effects: 1 hour after ingestion ( 13, [4]](#4)).
  • Medium to Long-term effects: Limited evidence is available on the medium-term effects of L-citrulline supplementation on strength and recovery.

Suggested Use and Dosage #

L-citrulline Malate for resistance exercise performance and recovery; 8 grams per day, taken 1 hour before exercise, has been used in research studies ( 13, [4]](#4)). The ratio of Citrulline to Malate used is unknown for these studies.

Safety and Precautions #

L-citrulline is generally well-tolerated when taken at recommended dosages for endurance. Mild side effects, such as gastrointestinal discomfort, may occur in some individuals ( 15).

Anecdotal Notes #

It’s speculated that the formulations of L-Citruline Malate can have quality control issues regarding purity, potentially containing less L-citrulline and more Malate because it’s cheaper to produce ( 10).

Additionally, there’s a blog post that ( 11) has indicated that Citruline Malate (CM) is not being commercially produced for some time now. What is being sold as Citrulline Malate is in fact a dry blend of Citruline and Malate, instead of chemically bonded (more expensive to produce). The blog concludes with the following:

There is research on citrulline but not much on supplementing with malic acid to replenish depleted levels as a Krebs cycle intermediary. I don’t think we can infer through the research on CM that the malic acid was the bioactive component since we can’t determine if the results came from the citrulline, the malic acid or a synergistic blend of the two.

These anecdotal findings align with this review from Gough LA et. al. of L-Citrulline Malate, questioning its effectiveness and also citing quality control issues, from the abstract of this study:

… the recent discovery of quality control issues with some manufacturers stated (i.e., citrulline:malate ratios).

General health #

Benefits #

  1. Enhanced immune function: L-arginine is known to play a crucial role in immune function by supporting the production of T-cells and promoting wound healing ( 7).
  2. Improved erectile function: L-arginine supplementation has been shown to improve erectile function in men with erectile dysfunction by increasing nitric oxide production and blood flow ( 8).
  3. Faster wound healing: L-arginine has been shown to accelerate wound healing by stimulating the production of collagen and other growth factors ( 7).
  4. Reduced symptoms of sickle cell disease (a blood disorder): L-arginine supplementation has been found to reduce pain and improve blood flow in patients with sickle cell disease ( 5).

Special Considerations #

  1. Medical conditions and medications: People with certain medical conditions, such as kidney or liver disease, or those taking medications that affect blood pressure or nitric oxide levels, should consult their healthcare provider before taking L-citrulline or L-arginine supplements.

  2. Pregnancy and breastfeeding: The safety of L-citrulline and L-arginine supplementation during pregnancy and breastfeeding is not well established. It is best to consult a healthcare provider before using these supplements during these periods.

Conclusion #

L-citrulline and L-arginine supplementation can offer various health benefits, such as improved cardiovascular health, enhanced immune function, and improved erectile function. L-citrulline has been shown to improve endurance and weight training performance, while L-arginine’s effects on exercise performance remain inconclusive.

The addition of Malate within L-Citrulline Malate (CM) seems to have some benefit for muscle soreness and recovery, but at the same time there are concerns around quality control of these supplements and the nature of the studies done with CM making it hard to draw firm conclusions on their efficacy. If you choose to go with CM, make sure that supplement provides the ratio of Citrulline to Malate as stated confirmed by a third party tested laboratory.

It seems that supplementing with L-Citrulline alone offers the most benefit supported by randomized controlled trials, dosages in the range of 2-6 grams per day for endurance and likely weight training. The dosages in the trials vary and it would require some experimentation what dosage would work best for you.

References #

1. Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., Spickler, W., Schulze, F., & Böger, R. H. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology, 65(1), 51-59. https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2125.2007.02990.x

2. Pahlavani, N., Jafari, M., Sadeghi, O., Rezaei, M., Rasad, H., & Rahdar, H. A. (2017). L-arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial. F1000Research, 3, 306. https://f1000research.com/articles/3-306

3. Suzuki, T., Morita, M., Kobayashi, Y., & Kamimura, A. (2016). Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. Journal of the International Society of Sports Nutrition, 13, 6. https://jissn.biomedcentral.com/articles/10.1186/s12970-016-0117-z

4. Pérez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research, 24(5), 1215-1222. https://pubmed.ncbi.nlm.nih.gov/20386132/

5. Morris, C. R., Kuypers, F. A., Lavrisha, L., Ansari, M., Sweeters, N., Stewart, M., Gildengorin, G., & Neumayr, L. (2013). A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica, 98(9), 1375-1382. https://pubmed.ncbi.nlm.nih.gov/23645695/

6. Bode-Boger, S. M., Muke, J., Surdacki, A., Brabant, G., Boger, R. H., & Frolich, J. C. (1998). Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vascular Medicine, 3(4), 309-316. https://pubmed.ncbi.nlm.nih.gov/14518608/

7. Witte, M. B., & Barbul, A. (2003). Arginine physiology and its implication for wound healing. Wound Repair and Regeneration, 11(6), 419-423. https://onlinelibrary.wiley.com/doi/10.1046/j.1524-475X.2003.11605.x

8. Stanislavov, R., & Nikolova, V. (2003). Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex & Marital Therapy, 29(3), 207-213. https://www.tandfonline.com/doi/abs/10.1080/00926230390155104

9. Gough LA, Sparks SA, McNaughton LR, Higgins MF, Newbury JW, Trexler E, Faghy MA, Bridge CA. A critical review of citrulline malate supplementation and exercise performance. Eur J Appl Physiol. 2021 Dec;121(12):3283-3295. doi: 10.1007/s00421-021-04774-6. Epub 2021 Aug 21. PMID: 34417881; PMCID: PMC8571142. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571142/

10. Everything you need to know about Pure Citrulline vs Citrulline Malate https://www.cardiffsportsnutrition.co.uk/blogs/articles/everything-you-need-to-know-about-pure-citrulline-vs-citrulline-malate

11. Citrulline vs. Citrulline Malate – We challenged the industry and it’s still happening! https://blog.nutrabio.com/2019/11/01/citrulline-vs-citrulline-malate-we-challenged-the-industry-and-its-still-happening/

12. Gonzalez AM, Trexler ET. Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature. J Strength Cond Res. 2020 May;34(5):1480-1495. doi: 10.1519/JSC.0000000000003426. PMID: 31977835. https://pubmed.ncbi.nlm.nih.gov/31977835/

13. Wax, B., Kavazis, A. N., Weldon, K., & Sperlak, J. (2015). Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. Journal of Strength and Conditioning Research, 29(3), 786-792. https://doi.org/10.1519/JSC.0000000000000670

14. Bailey, S. J., Blackwell, J. R., Lord, T., Vanhatalo, A., Winyard, P. G., & Jones, A. M. (2015). L-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology, 119(4), 385-395. https://journals.physiology.org/doi/full/10.1152/japplphysiol.00192.2014

15. Orozco-Gutiérrez, J. J., Castillo-Martínez, L., Orea-Tejeda, A., Vázquez-Díaz, O., Valdespino-Trejo, A., Narváez-David, R., … & Sánchez-Santillán, R. (2010). Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. Cardiology Journal, 17(6), 612-618. https://pubmed.ncbi.nlm.nih.gov/21154265/

16. Bode-Böger, S. M., Böger, R. H., Galland, A., Tsikas, D., & Frölich, J. C. (1998). L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. British Journal of Clinical Pharmacology, 46(5), 489-497. https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2125.1998.00803.x

17. Chen, J., Wollman, Y., Chernichovsky, T., Iaina, A., Sofer, M., & Matzkin, H. (1999). Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU International, 83(3), 269-273. https://onlinelibrary.wiley.com/doi/full/10.1046/j.1464-410x.1999.00906.x

Comments #

What have your experiences been with; L-Citrulline, or L-Citrulline Malate, or L-arginine?

Let me know in the comments, thanks for reading.