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L-Citrulline

Updated: Sep 8, 2023


l'citrulline

What is L-Citrulline?

L-citrulline is a non-essential amino acid that is most efficient in increasing plasma levels of arginine which is the main substrate for the synthesis of nitric oxide. Attributed to this, it has been marketed as a supplement that improves blood flow.


Which foods are naturally rich in citrulline?

In watermelon, citrulline content ranges from 3.9 mg/g to 28.5 mg/g of dry weight(1). Other sources include cantaloupe, bitter melon, cucumber, squash, and pumpkins.


L-citrulline versus citrulline malate

Citrulline Malate is formed through the combination of l-citrulline and malic acid. Through the tricarboxylic acid cycle, malic acid is dehydrogenated into oxaloacetate, one of the most critical controls of the rate of aerobic ATP production(2). The synergistic mechanisms of l-citrulline and malic acid may offer added benefits to athletic performance in comparison with solely supplementing with l-citrulline. However, more research is needed to directly compare l-citrulline and citrulline malate ingestion to assess if the addition of malic acid does offer added benefits to exercise performance.


How is citrulline created in the body?

Citrulline is created through two different pathways. First, the arginine pathway where the conversion of arginine into nitric oxide leaves citrulline as a byproduct, or the glutamine pathway which accounts for most of the circulating citrulline and is produced from the nitrogen contained in l-glutamine(3).


After consumption, citrulline circulates passively in the blood or is transferred to the kidneys for conversion into arginine.


Does supplementing with l-citrulline increase nitric oxide to thus improve blood flow?

L-citrulline supplementation has been marketed as a vasodilator stemming from the improvements in the l-arginine and nitric oxide pathways(4).


For instance, a study treated 8 healthy male subjects with 5.6g of l-citrulline per day and 7 participants with a placebo. The plasma citrulline, arginine, and the ratio of arginine to an endogenous inhibitor of nitric oxide synthase significantly increased in the l-citrulline group(5). Moreover, 22 trained males who consumed 2.4g of l-citrulline orally for 7 days significantly increased their plasma l-arginine levels(6).


Will this improve muscle oxygenation?

Muscle oxygenation is the rate of oxygen usage and supply to working muscle tissues. This is correlated with nitric oxide metabolism, as when blood flow increases, more oxygen is delivered to the working muscles.


For example, 18 participants consumed 6g of citrulline malate for 15 days. This resulted in a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise(7).


Will this increase blood flow in individuals with high blood pressure?

For hypertensive individuals, blood vessels may become constricted due to high blood pressure, thus, the reduction in blood pressure from l-citrulline supplementation in this case may help dilate the blood vessels to increase blood flow.


To illustrate this, a study analyzed aerobic exercise combined with citrulline supplementation. Randomly assigned hypertensive and sedentary volunteers ingested 6g of citrulline malate, as a result, blood pressure was reduced(8). In addition, a dose of 6g of l-citrulline regulated blood pressure via improved nitric oxide production in adults with prehypertension(9).


Should I supplement with l-arginine instead of l-citrulline?

Some studies suggest in a dose-dependent manner, l-citrulline does increase plasma l-arginine levels more effectively than supplementing with l-arginine(10,11).


Dosage Timing?

While there is some evidence that suggests taking L-citrulline approximately 40 to 60 minutes before exercise may be optimal for improving exercise performance(12,14), the optimal timing may vary depending on factors like metabolism and the type of exercise being performed.


Thus, we take l-citrulline about 30 minutes before we begin our hypertrophy or strength training and 60 minutes before a cardio workout. Ultimately, attributed to the experience we have using this supplement, we feel that this dosage timing is the best method that works for us.


Safe dosages?

First, citrulline malate supplement usually contains a ratio of 2 parts L-citrulline to 1 part malic acid, approximately 67% L-citrulline and 33% malic acid by weight. Therefore, to get 1 gram of L-citrulline from this supplement, you would need to take approximately 1.5 grams of the citrulline malate supplement.


Furthermore, to supplement with l-citrulline to enhance sports performance, studies use around 3g to 6g prior to a workout(13,14,15,16).


Studies have also shown tolerance of up to 15g of l-citrulline without any side effects, however, a lower fraction is absorbed and retained in the blood(17).


Anecdotally, we supplement with about 3g of l-citrulline pre-workout.


Review...

We recommend l-citrulline for anyone looking for an enhancement in blood flow and oxygen uptake during their workout.


Generally in a hypertrophy workout, as more oxygen and nutrients are needed, the heart pumps more blood to your working muscles creating a temporary pump-like effect. Therefore, regarding the transient hypertrophy(temporary pump) of the muscles, we notice a greater 'pump' when supplementing with l-citrulline. as well as a noticeable difference in vascularity.

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Also, all content contained within this article is for informational purposes only and is not intended to substitute the advice, diagnosis, or treatment from a qualified medical professional. Before taking l'citrulline, you should talk to your healthcare provider, especially if you have any medical conditions or are taking any medications. Your healthcare provider can help you determine a safe and effective dose for your individual needs.


References

(1) Rimando AM, Perkins-Veazie PM. Determination of citrulline in watermelon rind. J Chromatogr A. 2005 Jun 17;1078(1-2):196-200. doi: 10.1016. [PubMed]


(2) Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJ. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002 Aug;36(4):282-9. doi: 10.1136. [PubMed]


(3) Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober L. Almost all about citrulline in mammals. Amino Acids. 2005 Nov;29(3):177-205. doi: 10.1007. [PubMed]


(4) Figueroa, Arturo et al. “Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance.” Current opinion in clinical nutrition and metabolic care vol. 20,1 (2017): 92-98. doi:10.1097. [PubMed]


(5) Ochiai, Masayuki et al. “Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men.” International journal of cardiology vol. 155,2 (2012): 257-61. doi:10.1016. [PubMed]


(6) Suzuki, Takashi et al. “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 vol. 13 6. 19 Feb. 2016, doi:10.1186. [PubMed]


(7) Bendahan, D et al. “Citrulline/malate promotes aerobic energy production in human exercising muscle.” British journal of sports medicine vol. 36,4 (2002): 282-9. doi:10.1136/bjsm.36.4.282. [PubMed]


(8) Casonatto, J et al. "Citrulline malate supplementation might potentiate post-exercise hypotension in hypertensives: A 24-hour analysis." Science and Sports vol. 34,4 (2019): 261.e1-261.e9. doi: 10.1016. [Link]


(9) Qiu, J et al. "L-citrulline Supplementation Reduced Peripheral Blood Pressure in Chinese Adults with Prehypertension." Journal of Hypertension vol 30 (2012): 250. doi: 10.1097. [Link]


(10) Schwedhelm, Edzard et al. “Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.” British journal of clinical pharmacology vol. 65,1 (2008): 51-9. doi:10.1111. [PubMed]


(11) Agarwal, Umang et al. “Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice.” The Journal of nutrition vol. 147,4 (2017): 596-602. doi:10.3945/jn.116.240382. [PubMed]


(12) Glenn, Jordan M et al. “Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females.” European journal of nutrition vol. 56,2 (2017): 775-784. doi:10.1007/s00394-015-1124-6. [PubMed]


(13) Wax, Benjamin et al. “Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters.” Journal of strength and conditioning research vol. 29,3 (2015): 786-92. doi:10.1519/JSC.0000000000000670. [PubMed]


(14) 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. 31,4 (2021): 350-358. doi:10.1123/ijsnem.2020-0295. [PubMed]


(15) Trexler, Eric T et al. “Effects of Citrulline Malate and Beetroot Juice Supplementation on Blood Flow, Energy Metabolism, and Performance During Maximum Effort Leg Extension Exercise.” Journal of strength and conditioning research vol. 33,9 (2019): 2321-2329. doi:10.1519/JSC.0000000000003286. [PubMed]


(16) Allerton, Timothy D et al. “l-Citrulline Supplementation: Impact on Cardiometabolic Health.” Nutrients vol. 10,7 921. 19 Jul. 2018, doi:10.3390/nu10070921. [PubMed]


(17) Moinard, C et al. “Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study.” The British journal of nutrition vol. 99,4 (2008): 855-62. doi:10.1017/S0007114507841110. [PubMed]

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