Citrulline improves endurance and enhances recovery.
Amino acids are the fundamental building blocks of all tissue. Citrulline is a non-essential amino acid that’s made naturally by your body through a process that also produces NO or nitric oxygen from arginine (Schmidt et al, 1988).
Amino acids are divided into three groups; essential, semi-essential, and nonessential. Essential amino acids cannot be synthesized by your body, so they must be supplied through your diet and/or supplementation. Sem-essential amino acids are synthesized by the body but in low quantities. Non-essential amino acids can be made by your body, on demand (Lopez, Mohiuddin, 2024).
Nitric oxygen (NO) is an important signaling molecule in processes throughout your body. It functions as a neurotransmitter, a regulator of nutrient metabolism, inflammation, skeletal muscle perfusion, muscle fatigue, mitochondrial respiration, and a killer of bacteria, fungi, parasites and viruses, and a vasodilator (Shen et al, 1994; Bailey et al, 2009, Tschakovsky & Joyner, 2008; Larsen et al, 2011; Jones, 2016; Dominguez et al, 2018; Wu et al, 2021). It is believed that diminished availability of NO contributes to developing age- and lifestyle-related risk factors and diseases.
NO is one of the most crucial molecules when it comes to the health of our blood vessels for its role as a vasodilator, relaxing the muscular walls of the vessels, which then opens or widens blood vessels and arteries. In turn, this lowers blood pressure which increases blood flow to tissues, a very important benefit for athletes.
NO also neutralizes reactive oxygen species (ROS). ROS are produced as a normal product of cellular metabolism. A buildup of ROS in cells can be damaging and lead to cell death. A buildup of ROS can be detrimental to recovery and subsequent endurance.
The discovery of nitric oxide was monumental and netted Robert F Furchgott, Louis J Ignarro, and Ferid Murad a Nobel prize (Nicholls, 2019).
Citrulline elevates levels of nitric oxide, making it a very desirable aide to performance.
Citrulline has important health benefits on its own and is a benefit to athletic performance if taken consistently at a high enough dose. Citrulline taken acutely, or briefly, can benefit some types of athletic performances. We will present the research on citrulline and explain how it works in your body and how it enhances performance.
-Intake
Watermelon is a primary natural source of Citrulline. Its name is derived from Citrullus, the Latin name for watermelon (Koga & Ohtake, 1914; Wada, 1930). Other foods known to contain citrulline include pumpkins, cucumber, bitter melon, and gourdes (Rimando & Perkins-Veazie, 2005).
The concentration of l-citrulline in watermelon grown in the United States can range from 1.6 to 3.5 g/kg of fresh watermelon. As such, consumption of approximately 1–1.5 kg/day or 2.2–3.3 lbs/day of fresh watermelon would be needed to achieve the minimum effective dose of l-citrulline (3 g/day). Consumption of 3.3–5.0 kg/day (7.3–16.5 lbs/day) of fresh watermelon would be needed to achieve the maximum effective dose of l-citrulline (10 g/day) (Davis et al, 2011).
Since it is difficult to obtain L-citrulline from a conventional diet in sufficient amounts to enhance sports performance, it is easier to take a few tablets of L-citrulline before exercise as an ergogenic aid.
Tip: If your body makes any chemical, it can only do so if it has its chemical tools or its chemical tool kit to work with. This tool kit is generally known as a precursor. Thus, that is why you supplement in addition to eating correctly, but don’t forget to supplement safely. Supplementing with Arginine is hard on the liver and quickly leads to bowel distress. Citrulline is bowel tolerated and liver tolerated (Grimble, 2007).
There is no upper limit to citrulline intake, as the body expels the excess in urine. Suggested dosage for athletes in competition is nominally 6 to 8 grams of L-Citrulline and 3 to 4 grams of Lysine just after your workout along with a ¼ teaspoon of sugar (to stimulate the insulin response which enhances repair). Lysine helps the body form collagen, which is important for bone and connective tissue growth and maintenance. Many athletes make their post workout smoothie and add the above to it.
-Types of Citrulline Supplements
Citrulline is considered safe for oral use and has no identified toxicity (Rougé et al, 2007). No side effects have been reported from citrulline administration at doses up to 15g (Moinard et al, 2008).
Citrulline exhibits good bioavailability thanks to its ability to be handled by a wide number of amino acid transporters (Moinard et al, 2008; Bahri et al, 2008).
There are two major forms of citrulline in dietary supplements:
While the two forms of may produce some similar effects, citrulline malate is more common in sports supplements.
Citrulline may affect the way certain drugs work in your body. Do not take this supplement if you are taking:
-Dosage
Research has established that citrulline is effective when taken at least seven days before an anaerobic or aerobic performance event. Citrulline is ineffective if taken as an acute dose, just prior to an aerobic event. We will review that literature.
Taking 3 grams of L-citrulline three hours before an event or taking 9 grams 24 hours prior to a treadmill test showed no improvements (Hickner et al, 2006). A randomized double-blind study examined the effect of a pre-exercise dose of citrulline (6 grams) as watermelon juice (to provide 1g of citrulline), or placebo (7.5% sucrose placebo drink) on performance markers. They found no significant improvement when the citrulline was taken just prior (Cutrufello et al, 2015). In another study, ten well trained athletes took either 12 grams of citrulline or a lemon sugar-free cordial (placebo) 60 minutes before completion of two exercise trials. While body measurements showed significant increases in citrulline, there were no ergogenic benefits from an acute dose (Cunniffe et al, 2016).
Martínez-Sánchez et al, 2017) also demonstrated that consuming 500-ml watermelon juice enriched with L-citrulline (3.45-g L-citrulline) 120 minutes before performing a half-marathon time trial did not improve completion times or ratings of perceived exertion compared with a placebo in amateur male runners. Recreationally active men and women were recruited to take part in an isokinetic chair protocol, based on German Volume Training (GVT) whereby participants attempted to perform 10 sets of 10 repetitions against a force representing 70% of their peak concentric force. Subjects were provided with either the treatment (8 g of Citrulline Malate as 4.21 g citrulline, 3.79 g malate), or placebo 6 g of Citric acid just prior to exercise. Giving the dose just prior to exercise produced no performance benefits (Chappell et al, 2018). 18 resistance trained men and women were given either 8 grams of L-citrulline or a placebo in a cross-over fashion one hour prior to testing with an isometric mid-thigh pull test, a ballistic bench press protocol and a strength-endurance bench press protocol. There was no benefit from a single 8 gram dose (Gonzales et al, 2023). A recent review of research on short-term, acute intake of citrulline, showed that there is no significant benefit for endurance performance tasks (Harden et al, 2023).
A review of the literature in 2020 reported that chronic dosing (>7 days) seems to be more effective than an acute single-dose protocol for enhancing exercise performance. The minimum effective dose seems to be approximately 3 g/day of L-citrulline, while the maximum effective dose may be as high as 10–15 grams/day (Gonzalez & Trexler, 2020). A study where 2 g/day of citrulline for 8 weeks did not improve bench press performance (Hwang et al, 2018) suggests that 2 grams a day is insufficient.
Below are recommendations for specific uses:
The dose varies depending on form because 1.75 grams of citrulline malate provides 1 gram of L-citrulline. The remaining 0.75 grams are malate.
-Performance
Given the multifaceted role of nitric oxide in vasodilation and other exercise-related physiological processes, there is great interest in using citrulline supplementation to elevate nitric oxide and to enhance endurance and high-intensity exercise performance. The improvement in the vascular system and increased blood flow throughout your body allows for improved muscle oxygen utilization, thereby enhancing exercise performance (Wang et al, 2001; Smith et al, 2002).
There is a wealth of research documenting the benefits of citrulline for athletic performance. The research falls in both the anaerobic aerobic areas as well as endurance area.
Anaerobic and aerobic
10 healthy men were given 6 grams/day of L-citrulline and 6 grams/day of l-arginine, and a placebo. for a week. On days 6 and 7, they completed cycling exercises. The cyclists taking citrulline were able to cycle for 12% longer before exhaustion than those taking a placebo. It was postulated that improving O2 availability and distribution within the muscle microvasculature enhanced their performance during exercise (Bailey et al, 2015).
The same research group investigated the benefits of taking watermelon juice equal to 3.4 grams of citrulline, with apple juice functioning as a placebo. On day 14, the participants were tested. Those who received watermelon juice showed higher blood levels of L-citrulline, L-arginine, and nitrate, as well as having higher blood pressure. During the exercise, they also showed higher skeletal muscle oxygenation but were not significantly better on the exercise trial. This amount of watermelon juice supplemented was not effective to improve exercise performance (Bailey et al, 2016).
Male cyclists were given 2.4 grams/day of L-citrulline or placebo orally for 8 days. On day 8, they completed a 4 km cycling time trial. Those who received L-citrulline showed increased arginine levels and a reduced completion time of 1.5%, compared with placebo. The improved TT performance with L-citrulline was the consequence of significantly greater PO (Power output) for the same VO2. (Power output is how much force can be produced in a certain amount of time.). In addition, they reported significantly improved feelings of muscle fatigue and concentration immediately after exercise (Suzuki et al, 2016).
A study of male collegiate track athletes who took 3 g of citrulline daily for seven days showed increased concentrations of blood levels of nitric oxide, an improved pedaling speed and improved average power output (Terasawa et al, 2019).
Cyclists who were given 6 grams of citrulline per day for seven days demonstrated improvements in time trial performance of 5.2%, average power output, heart rate increase, and rate of perceived exertion (RPE) (Stanelle et al, 2020). That dose provided a direct benefit to endurance performance in trained athletes.
Muscle Strength, Power & Endurance
Citrulline possesses a highly specific metabolism that may be used to deliver nitrogen for protein homeostasis in peripheral tissues and functions as an arginine precursor. Recent data have suggested that citrulline, stimulates protein synthesis in skeletal muscle (Osowska et al, 2006; Bahri et al, 2014).
In contrast to aerobic performance, it appears that acute doses of citrulline may have an impact on strength events. 41 resistance-trained men took 8 grams of citrulline malate (CM) one hour before exercise. The iteration to failure was improved in all sets of barbell bench presses (except for the first two sets). This increase was positively correlated with the number of sets, achieving 52.92% more repetitions and the 100% of response in the last set. A significant decrease of 40% in muscle soreness at 24 hours and 48 hours after the pectoral training session and a higher percentage response than 90% was achieved with citrulline supplementation. They concluded that CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve postexercise muscle soreness. Thus, athletes undergoing intensive preparation involving a high level of training or in competitive events might profit from taking citrulline (Perez-Guisado et al, 2010).
Another study investigated the potential of watermelon juice as a functional drink for athletes. 7 men active in sports participated in the study, taking 500 mL of natural watermelon juice (1.17 g of L-citrulline), enriched watermelon juice (4.83 g of L-citrulline plus 1.17 g from watermelon), and placebo. Both watermelon juices helped to reduce the recovery heart rate and significantly reduced muscle soreness after 24 hours (Tarazona-Diaz et al, 2013).
Resistance-trained male subjects were given 8 grams of citrulline malate prior to resistance exercise. Those who received the citrulline performed a significantly higher number of repetitions during all 3 exercises compared with placebo group and had decreased fatigue (Wax et al, 2015). This same research group found that citrulline malate increased upper body resistance performance in college age males (Wax et al, 2016).
Japanese males took 2.4 g/day of citrulline for 7 days and showed enhanced cycling performance as a result of significantly greater Power Output for the same VO2 max, as well as significantly improved feelings of muscle fatigue, and concentration after exercise (Suzuki et al, 2016). Soccer players took L-citrulline (1.2 g/day) and L-arginine (1.2 g/day) for six days, and an hour before exercise on the seventh day. Those who received supplements showed significantly greater power output (Suzuki et al, 2019).
Elite taekwondo athletes ingested both Arg and Cit between two matches. They reported a reduction in exercise-induced fatigue, and significantly better reaction times compared to those who received a placebo (Chen et al, 2016).
Fifteen females took 8 grams of citrulline and 8 grams of dextrose one hour before strength exercise. The acute CM supplementation increased upper- and lower-body resistance exercise performance and decreased the perceived exertion during upper-body exercise. These data indicate that athletes competing in sports with muscular endurance-based requirements may potentially improve performance by acutely supplementing CM (Glenn et al, 2017). However, acute supplementation does not consistently improve performance. 12 recreationally trained participants were given 8 grams of citrulline malate, placebo, and no drink, when they visited the lab on 3 separate days, all separated by 1 week. At the same time, they performed one high-intensity exercise trial in a listed order. They found administration of citrulline malate just prior to exercise was ineffective in improving performance or alleviating fatigue (Farney et al, 2019).
Figueroa (et al. 2017) demonstrated that 8 weeks of L-citrulline 6 g/day in conjunction with whole-body vibration exercise training (WBVT) enhanced leg lean mass gains above the effect of WBVT alone.
Citrulline supplements, 3 grams/day or .04g/kg body weight, were given to 22 participants aged from 60-73 years. Walking speed significantly improved in that group, when compared to participants who received a placebo. Additionally, those who received citrulline showed improvements in markers of muscle damage toward the end of the six week intervention (Caballero-Garcia et al, 2021).
A study of trained swimmers and triathletes who took 8 grams of citrulline, arginine or placebo per day for eight days showed no difference in 200 meter and 100 meter time trial between groups. These findings do not support the use of L-citrulline or L-arginine supplementation as ergogenic aids for swimming performance. It was concluded swimming requires more muscle participation than land-based exercises (i.e., walking or running (Esen et al, 2022).
A randomized, double-blind study looked the effects of 4 weeks of citrulline supplementation followed by 4 weeks of combined citrulline supplementation with SVLIRT (a specific workout routine) on leg vascular function and muscle strength in 24 sedentary, hypertensive, postmenopausal women. The findings show that 4 weeks of CIT supplementation alone improved leg endothelial function and leg curl strength, and when added with SVLIRT, there was an additive effect on leg lean mass and curl strength (Dillon et al, 2023).
6 males, average age 22.2 were given L-citrulline and glutathione or a placebo for eight days. Three timed treadmill runs to exhaustion (TTE) were performed at 90%, 100%, and 110% PV. After a 14-day washout, participants repeated the same procedures, ingesting the opposite treatment. Those who took the citrulline blended with glutathione showed augmented blood flow and improved TTE by ~10 seconds at 110% intensity, signifying L-citrulline supplementation may have positive effects on high-intensity exercise performance in aerobically trained males (Cabre et al, 2023).
A recent meta-analysis suggested that acute Cit supplementation confers a significant performance benefit for high-intensity strength and power tasks in comparison to placebo. The effect size was small (0.20), but may be relevant to high-level athletes, in which competitive outcomes are decided by small margins (Trexler et al, 2019). According to another review study, taking a single acute dose of 8 g of citrulline malate one hour prior to exercise in resistance-trained men and women may improve dynamic muscle endurance and strength performance (Gonzalez & Trexler, 2020).
Two recent reviews of the literature on citrulline and arginine supplementation on cardiovascular health and athletic performance was recently completed. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis when taking 0.075 g or 6 g doses of Arg supplement per body weight. However, when taking 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion (Nyawose et al, 2022) Park et al, 2023).
-Muscle Building
Although citrulline isn’t an amino acid used directly to build muscles, it has been shown to increase protein synthesis by stimulating an important signaling pathway involved in muscle building (NEAA) (Osowska et al, 2006). The benefit of citrulline on blood vessels, through it being a precursor of NO, may play a role in muscle building (Figueroa et al, 2017; Breuillard et al, 2015). The widened vessels contribute to increased blood flow, oxygen, and nutrient delivery to active muscles.
Eight healthy participants were investigated in a crossover study in which, following 3 days of standardized low protein intake, L-citrulline or a NEAA (non-essential amino acid) mixture was given orally over the course of 8 hours. Fractional synthesis rates (FSR) of muscle proteins were high in those who took the citrulline (Jourdan et al, 2015).
Nine young adult men took 6 g of citrulline malate or placebo on two occasions of a high intensity workout, separated by a seven-day washout period. They did not find any improvement in muscle recovery, though it is likely that the dose was too infrequent (Da Silva et al, 2017). Similarly, men and women who took 8 g of L-citrulline one hour prior to resistance exercise did not show improved muscle force, endurance or oxygenation (Gonzalez et al, 2018).
-Human Growth Hormone (HGH)
Human growth hormone (HGH) is instrumental in speeding up the body’s healing processes following an injury or intense exercise. HGH helps to maintain, build, and repair healthy tissue in the brain and other organs. HGH rises after exercise for this purpose (Schoenfeld, 2013). The HGH is then converted to igf-1 which is a critical catalyst to promote healing (Uyanga et al, 2022).
Citrulline helps stimulates your pituitary to produce HGH. Seventeen male pre-professional cyclists were randomly assigned receive 6 g L-citrulline-malate 2 hours prior to exercise or a placebo. Growth hormone increased after exercise in both groups, although the increase was higher in the citrulline-malate supplemented group (p < 0.05) (Sureda et al, 2010).
-Heart Benefits
Citrulline offers major benefits for heart health as it functions as a precursor for nitric oxide (NO) which causes vasodilation of blood vessels by relaxing the smooth muscle cells that constrict them (Chopra et al, 2011; Quillon et al, 2015; Allerton et al, 2018). Short-term treatment for 7–14 days with l-citrulline (5.6 g/day) reduced arterial stiffness in healthy and overweight middle-aged men (Ochiai et al, 2012; Sanchez-Gonzales et al, 2013).
When people who have heart disease or are at risk of heart disease have consumed 5.6 grams/day L-citrulline for seven days or longer, the ability of their arteries to widen improves and arterial stiffness is reduced (Morita et al, 2013). A 6-week intervention study with 6 g per day of watermelon extract supplementation in postmenopausal obese women receiving hypertension treatment, resulted in a decrease in arterial stiffness and aortic SBP, as well as a decrease in blood pressure pulse wave reflection (Figueroa et al, 2013.
Reduced Blood Pressure
Studies conducted of adults with high blood pressure or other heart conditions showed that participants’ blood pressure reduced by 4–16% after eight weeks of taking 3g/day of L-citrulline (Orozco-Guttierez et al, 2010). Women taking 6g/day of L-citrulline improved their blood pressure (Wong et al, 2016). What’s more, in a small study examining 12 adults with normal blood pressure, researchers found that citrulline reduced blood pressure by 6–16% after 7 days of intake (Alsop & Hauton, 2016). A systemic review and meta-analysis of clinical trials showed that L-citrulline supplementation may reduce systolic blood pressure, only in studies that used doses greater or equal than 6 grams/day (Barkhidarian et al, 2019).
Nine subjects who took a watermelon supplementation containing L-citrulline/L-arginine 1.35 grams/ twice a day, for six weeks separated by a 4-week washout period. The alternative was placebo. Blood pressure and aortic wave were all lower in those who received the supplement (Figueroa et al, 2011). The same research group later studied 14 middle-aged adults with pre- and hyper-tension in a cross-over design where they received watermelon supplementation of 6 grams/ day (L-cittruline/L-arginine) or placebo for six weeks separated by 2-week washout period, followed by a crossover. The results showed that the watermelon extract supplementation reduced all measures of hypertension (Figuero et al, 2012). A third study of obese, post-menopausal women diagnosed with hypertension, treated with 6 weeks of watermelon supplementation showed reduced arterial stiffness and aortic systolic blood pressure (Figuero et al, 2013).
Another group of investigators recently reported that adults with heart failure had improvements in left ventricular ejection fraction, and endothelial function after treatment with oral CIT for 4 months (Balderas-Munoz et al, 2012)
-Modulates Inflammation
l-citrulline supplementation is also likely to provide indirect benefits to vascular health by modulating chronic low-grade inflammation. Oral l-citrulline ingestion has been shown to reduce serum inflammatory cytokine concentrations, such as IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein in both aged animals (Joffin et al, 2015), and humans (Barkhidarian et al, 2016).
These studies suggest that l-citrulline supplementation is likely to have great clinical benefits, especially in the context of inflamm-aging, the chronic low-grade inflammation associated with aging (Francheschi et al, 2000) which is a well-known aggravating factor for cardiometabolic disorders (Lopez-Candales et al, 2017), poor vascular health (Guzik & Touyz, 2018) and overall morbidity and mortality (Xia et al, 2015)
-Reduces Lactate Buildup
During high-intensity exercise, ammonia builds up in skeletal muscle, leading to the formation of lactate which contributes to muscle exhaustion. Citrulline improves the aerobic pathway by maintaining low plasma lactate concentrations. In mice, citrulline significantly increased the exercise to exhaustion, and repressed the blood ammonia levels, resulting in significantly lower lactate levels (Takeda et al, 2011). Human studies have shown that supplementation with citrulline could enhance time-trial performance in two consecutive days in endurance runners, possibly through the the prevention of excess hyperammonemia (Cheng et al, 2016).
Cit supplements improved the aerobic pathway, lowered plasma lactic acid concentrations during half marathon races, and alleviated post-race muscle soreness (Martinez-Sanchez et al, 2017). 22 active handball players were given citrulline malate and subjected to intense training for 4 weeks, 4 days a week, mainly pre-season strength and technique training. In this training period, the athletes were given citrulline malate 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g for dinner while the placebo group athletes were given only placebo in the same dosage and the same color at the same time. The study showed that supplement of cit-mal efficiently decreased blood lactate levels immediately after exercise by 49.8% (Kiyici et al, 2017).
A systematic review and meta-analysis determined the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels. The most frequent dosage used in the studies was 8 g of citrulline malate. The review showed that citrulline supplementation significantly reduced RPE (rating of perceived exertion), muscle soreness 24-h and 48-h after post-exercise. This meta-analysis did not find an overall effect on reducing blood lactate levels (Rhim et al, 2020).
-Mitochondrial Growth
Several studies have shown that the generation of nitric oxide can increase mitochondrial biogenesis by activating PGC1-α (Nisoli et al, 2003; Valerio et al, 2011). PGC1- α is a regulator of mitochondrial growth and controls muscle fiber adaptation to exercise. In a recent study, supplementing l-citrulline (250 mg/kg) for 15 days in mice resulted in elevations in PGC1-α mRNA and protein expression in hindlimb and forelimb muscles (Villareal et al, 2018). Importantly, these elevations in PGC1-α mRNA and protein expression were associated with improvements in exercise performance as measured by time to exhaustion during a standardized swim test (Giannesini et al, 2011)
Summary
Citrulline is an amino acid that is well tolerated and offers many benefits to athletes. It improves blood flow, lowers blood pressure, stimulates muscle protein synthesis and mitochondrial growth, modulates inflammation, reduces soreness, and regular intake can improve performance. It stimulates HGH which contributes to healing and recovery from workout.
The research indicates that at least 6 grams daily is most effective, and depending on your event, it should be taken daily at least a week prior to competing.
Be sure to study the label of the citrulline you buy, to ensure how much citrulline you are getting in the capsule.
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NCAA Track & Field
Carolin, a German athlete, joined the NCAA track and field scene, opting to compete for UW-Parkside from the fall of 2021. Following several weeks of participation in cross country, Carolin introduced vitamin K and vitamin D into her supplement routine. Through consistent effort and dedication, she successfully lowered her 800-meter personal record during that season from 2:14 to 2:09, earning her a spot at the D2 indoor nationals, where she secured an 11th-place finish nationally. Post-MBA graduation, Carolin continues her athletic journey as a member of the LG Olympia Dortmund track & field team in Germany. In the 2023 outdoor season, she qualified for the German outdoor nationals, achieving a commendable 16th place in the 800-meter event. Pursuing her fitness aspirations, Carolin remains dedicated to her goals, aided by the support of Ultra K, aligning with the brand's mission to assist athletes in realizing their genuine potential.
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