- 1. Introduction
- 2. Physiological role of citrulline
- 3. Primary benefits of citrulline (malate) supplementation
- 4. Possible side effects of citrulline supplementation
- 5. Who should or should not use citrulline
- 6. When to take citrulline
- 7. Recommended dosing
- 8. Citrulline Malate FAQs
- About the physiological role and benefits of citrulline.
- Who should consider taking a citrulline supplement.
- When to take citrulline malate, and what the recommended dosage is.
Citrulline is a nonessential alpha-amino acid that is not coded for by human DNA but is still present in certain proteins and the urea cycle (either as a by-product of arginine oxidation or from reaction of carbamoyl phosphate and ornithine). Citrulline appears to have a variety of synergistic effects with other popular peri-workout supplements, such as branched-chain amino acids (BCAAs).
It is naturally produced in the rind and flesh of watermelon and is gaining ground as a useful ingredient in the field of dietary/sports supplements.
Physiological role of citrulline
Citrulline plays a variety of physiological roles, but is primarily relegated to augmentation of nitric oxide-dependent signaling. (1) Citrulline is manufactured by a variety of other amino acids in the liver and is an important component of the urea cycle; the urea cycle facilitates the elimination of ammonia and other nitrogenous toxins from the blood (most of which takes place in the liver of mammals). Nitrogen metabolites accrue from digestion, absorption, and metabolism of proteins.
Oral citrulline supplementation has been shown to increase increase plasma arginine concentration and thus enhances production of arginine-derived metabolites (i.e. nitrite, ornithine, creatinine, etc). (2) As aforementioned, this is crucial as synthesis and elimination of urea is necessary for removing toxic nitrogen metabolites from the body. Citrulline works along with citric acid, aspartic acid, and magnesium to improve nitrogen metabolite excretion.
A rare disorder in humans called citrullinemia may cause buildup of ammonia in the blood; this occurs when there is a deficiency of the enzyme necessary to catalyze the [citrulline-arginine] reaction of the urea cycle. Research seems to indicate that zinc supplementation can improve the conversion of citrulline to arginine in the liver and lower blood ammonia levels. (3)
Moreover, since pyridoxine (vitamin B-6) activates transaminases (i.e. enzymes that convert an amino acid to a different amino acid) in the urea cycle, it may be useful to supplement with if there is a suspected malfunction in the liver. As always though, these clinical abnormalities should be addressed by your personal care physician.
Primary benefits of citrulline (malate) supplementation
Citrulline supplementation, generally in malic acid salt form, has been garnering attention in the realm of physical performance enhancement and its benefits are numerous. Aside from being a necessary biomolecule in the urea cycle, citrulline may enhance health and performance by:
- Increasing intracellular NO production which is a positive regulator of vasodilation and blood flow (2)
- Enhancing the utilization of essential amino acids during exercise (1)
- Improving recovery time after exercise by attenuating delayed-onset muscle soreness (4)
- Enhancing elimination of toxic nitrogen metabolites (2)
- Increasing growth hormone levels to a higher degree in individuals after resistance training as compared to a placebo group (1)
- Reducing/inhibiting the increase in plasma insulin levels that usually arises after high-intensity exercise (3)
Possible side effects of citrulline supplementation
Thankfully, citrulline is a rather safe compound and the side effects are limited and generally benign. The most prevalent side effect for people supplementing with citrulline tends to be gastrointestinal distress, but this can be ameliorated by taking citrulline on an empty stomach.
Who should or should not use citrulline:
- Physique competitors
- Athletes involved in aerobic and/or anaerobic events/sports
- Those looking for increased blood flow and “pumps” during training
- Avoid use if you have citrullinemia as this would only compound the issue
When to take citrulline:
- Optimally, citrulline should be ingested about 15-30 minutes before training.
- May also take citrulline during and/or after training if desired
- Start with a once-daily dose of 6-7g
- If desired, dose may be increased to 15-20g split into multiple doses throughout the day
Citrulline Malate FAQs:
Q: Can I just eat watermelon rather than supplementing with citrulline?
A: Most of the citrulline content in watermelons is found in the rind of the fruit, therefore it is not very practical to obtain the doses of citrulline suggested herein through diet.
Q: Is it true citrulline may enhance libido and treat impotence?
A: This is actually another nice “benefit” of citrulline supplementation as the increase in nitric oxide will relax blood vessels and increase blood flow (which can help improve erections, among other things).
Q: I’ve heard citrulline should be taken on an empty stomach, is this true?
A: This is likely due to the rare occurrence of stomach distress that may occur after ingesting citrulline; it is fine to take citrulline at meal times if you tolerate it well.
Q: How long does it usually take for me to notice the effects of citrulline?
A: This will vary for most individuals, but acute effects such as endotoxin removal will happen after the first dose; more latent benefits such as strength increases and decreased DOMS may take a few weeks to notice.
1) Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons A. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010 Sep;110(2):341-51. doi: 10.1007/s00421-010-1509-4. Epub 2010 May 25. PubMed PMID: 20499249.
2) Wijnands KA, Vink H, Briedé JJ, van Faassen EE, Lamers WH, Buurman WA, Poeze M. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5):e37439. doi: 10.1371/journal.pone.0037439. Epub 2012 May 29. PubMed PMID: 22666356; PubMed Central PMCID: PMC3362574.
3) Marchesini, G., Fabbri, A., Bianchi, G., Brizi, M., & Zoli, M. (1996). Zinc supplementation and amino acid‐nitrogen metabolism in patients with advanced cirrhosis. Hepatology, 23(5), 1084-1092.
4) Pérez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. The Journal of Strength & Conditioning Research, 24(5), 1215-1222.
5) Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006 Apr;38(4):660-6. PubMed PMID: 16679980.