Citrulline is a naturally occurring amino acid that plays a vital role in various physiological processes within the human body. Unlike some amino acids, citrulline is classified as a nonessential amino acid, meaning that our bodies can produce it even if it is not obtained directly from our diet. Citrulline was first identified in watermelon (Citrullus vulgaris) from which it gets its name. It is also found in other foods such as cucumbers, pumpkins, and gourds. However, the quantities present in food are usually not sufficient to achieve the levels used in clinical studies, hence the use of citrulline supplements.

One of the main functions of citrulline is its involvement in the urea cycle, a critical process for removing ammonia from the body. This cycle converts ammonia, a toxic byproduct of protein metabolism, into urea, which is then excreted through urine. Citrulline acts as an intermediate in this cycle, assisting in the conversion of ammonia into urea, thereby helping to maintain nitrogen balance and protect the body from ammonia toxicity. This function is particularly important for individuals with certain genetic disorders affecting the urea cycle.

Beyond its role in the urea cycle, citrulline is converted into another amino acid called arginine in the kidneys. Arginine is a precursor to nitric oxide, a molecule that plays a crucial role in vasodilation, the process of relaxing and widening blood vessels. This property of nitric oxide makes citrulline particularly interesting for its potential cardiovascular benefits, including improved blood flow and reduced blood pressure. Due to these effects, citrulline has garnered attention in the fields of sports nutrition and cardiovascular health.

Studies have shown that citrulline supplementation can increase plasma arginine levels more effectively than arginine supplements themselves. This is because citrulline bypasses the liver's extensive first-pass metabolism that arginine undergoes, making it a more efficient precursor for raising arginine levels in the blood. This characteristic makes citrulline a promising supplement for various health benefits, ranging from enhanced exercise performance to better cardiovascular health.

Citrulline is used for several health purposes, primarily due to its ability to increase nitric oxide production and improve blood flow. In the realm of sports nutrition, citrulline is often utilized to enhance exercise performance and reduce muscle fatigue. Studies have demonstrated that citrulline malate, a compound that combines citrulline with malic acid, can improve athletic performance by increasing the number of repetitions in strength training exercises and enhancing overall endurance during high-intensity workouts. For example, a study published in the Journal of Strength and Conditioning Research found that participants who took citrulline malate were able to perform significantly more repetitions during upper-body resistance exercises compared to those who took a placebo.

In addition to its benefits for athletes, citrulline is also used for cardiovascular health. Its role in nitric oxide production helps to relax and widen blood vessels, which can improve blood flow and reduce blood pressure. A meta-analysis published in Current Hypertension Reports reviewed multiple clinical trials and found that citrulline supplementation significantly reduced both systolic and diastolic blood pressure in adults. This highlights its potential as a non-pharmacological intervention for managing hypertension.

Citrulline has also been explored for its potential benefits in treating erectile dysfunction (ED). Since nitric oxide is crucial for achieving and maintaining an erection, increasing nitric oxide levels through citrulline supplementation can help improve erectile function. A study in the journal Urology reported that men with mild ED who took citrulline supplements experienced improvements in erectile hardness compared to those who took a placebo.

Furthermore, citrulline is being investigated for its potential to enhance cognitive performance and reduce mental fatigue. While research in this area is still in its early stages, some preliminary studies suggest that the improved blood flow and oxygen delivery to the brain resulting from increased nitric oxide production could have positive effects on cognitive function and mental clarity.

Overall, the growing body of research supports the various uses of citrulline in improving exercise performance, supporting cardiovascular health, managing erectile dysfunction, and potentially enhancing cognitive function. However, more extensive and long-term studies are needed to fully understand its benefits and mechanisms of action.

Citrulline primarily functions through its conversion into arginine, which subsequently leads to the production of nitric oxide (NO). This process begins in the intestines, where citrulline is absorbed into the bloodstream and transported to the kidneys. In the kidneys, citrulline is efficiently converted into arginine, an amino acid that serves as a precursor for nitric oxide synthesis. Nitric oxide is a key signaling molecule that plays a crucial role in various physiological processes, most notably vasodilation—the relaxation and widening of blood vessels.

The mechanism of action for citrulline revolves around the L-arginine-NO pathway. When arginine is converted to nitric oxide by the enzyme nitric oxide synthase (NOS), it facilitates the relaxation of smooth muscle cells in the blood vessels. This relaxation leads to vasodilation, which improves blood flow and reduces blood pressure. Enhanced blood flow is beneficial not only for cardiovascular health but also for muscle performance during exercise, as it allows for better delivery of oxygen and nutrients to muscle tissues. A study published in the British Journal of Clinical Pharmacology demonstrated that citrulline supplementation effectively raises plasma arginine levels and enhances NO-dependent signaling in a dose-dependent manner.

In addition to its role in nitric oxide production, citrulline is involved in the urea cycle, a metabolic pathway that helps detoxify ammonia, a byproduct of protein metabolism. Ammonia is converted into urea in the liver and then excreted through the urine. Citrulline acts as an intermediate in this cycle, facilitating the conversion of ammonia into urea and thereby reducing ammonia levels in the blood. This function is particularly important during intense exercise when ammonia levels can rise significantly, contributing to muscle fatigue. By aiding in ammonia clearance, citrulline helps delay the onset of fatigue and improve exercise performance.

Moreover, citrulline's ability to enhance arginine levels can also support protein synthesis and muscle growth. Arginine is a precursor for the synthesis of creatine, a compound that plays a critical role in energy production within muscle cells. By increasing arginine availability, citrulline supplementation can potentially enhance creatine synthesis, thereby supporting muscle strength and growth. This multifaceted mechanism of action makes citrulline a versatile supplement with wide-ranging benefits for both athletic performance and overall health.

In summary, citrulline works through its conversion to arginine, leading to increased nitric oxide production, improved blood flow, and reduced blood pressure. It also plays a crucial role in the urea cycle, helping to detoxify ammonia and delay muscle fatigue. These mechanisms collectively contribute to citrulline's benefits in enhancing exercise performance, supporting cardiovascular health, and promoting muscle growth.

Citrulline supplementation is utilized in both men's and women's health, but there are some differences in how it is applied and the specific benefits it offers to each gender. These differences often stem from varying physiological needs and health concerns prevalent in men and women.

In men’s health, citrulline is frequently used to support cardiovascular health and improve exercise performance. One notable application is in the management of erectile dysfunction (ED). Since nitric oxide plays a crucial role in achieving and maintaining an erection by facilitating blood flow to the penile tissues, citrulline's ability to increase nitric oxide production makes it an attractive supplement for men experiencing mild to moderate ED. A study published in the journal Urology found that citrulline supplementation led to significant improvements in erectile function in men with mild ED. Additionally, citrulline can enhance athletic performance by increasing blood flow and oxygen delivery to muscles, which is particularly beneficial for men engaged in high-intensity resistance training and endurance sports.

For women, citrulline is often used to support cardiovascular health and improve exercise performance, similar to its use in men. However, women may also benefit from citrulline's potential effects on muscle recovery and reducing exercise-induced fatigue. Women generally have different muscle recovery needs and may experience higher levels of fatigue due to hormonal fluctuations throughout the menstrual cycle. Citrulline supplementation can help by facilitating better blood flow and nutrient delivery to muscles, thereby enhancing recovery and reducing soreness. A study in the European Journal of Applied Physiology demonstrated that citrulline-malate supplementation enhanced amino acid utilization and reduced muscle soreness following intense exercise, which can be particularly beneficial for women.

Another area where citrulline may be beneficial for women is in the management of menopausal symptoms. Menopause is associated with a decline in nitric oxide production, which can lead to cardiovascular issues and reduced blood flow. By increasing nitric oxide levels, citrulline can help mitigate some of these effects, potentially improving cardiovascular health and overall well-being during and after menopause. While research in this area is still emerging, the potential benefits of citrulline for menopausal women are promising.

Overall, while the core benefits of citrulline—such as improved blood flow, enhanced exercise performance, and better muscle recovery—are applicable to both men and women, the specific applications and health concerns addressed by citrulline supplementation can vary between genders. For men, the focus is often on cardiovascular health and erectile function, whereas for women, the emphasis may be on muscle recovery, reducing fatigue, and supporting cardiovascular health during menopause.

The appropriate dosage of citrulline can vary based on the specific health goals and individual needs. However, general guidelines have been established through clinical research to help determine effective dosages for various applications, such as enhancing exercise performance, improving cardiovascular health, and managing erectile dysfunction.

For enhancing exercise performance and reducing muscle fatigue, citrulline malate is commonly used. Research suggests that a dosage of 6 to 8 grams of citrulline malate taken approximately 30 to 60 minutes before exercise can be effective. A study published in the Journal of Strength and Conditioning Research found that this dosage improved performance in high-intensity resistance exercises by increasing the number of repetitions and reducing muscle soreness post-exercise. Athletes and individuals engaging in intense physical activities may benefit from this pre-workout supplementation to enhance endurance and recovery.

For cardiovascular health, particularly for lowering blood pressure and improving blood flow, a slightly lower dosage may be sufficient. Studies indicate that a daily dosage of 3 to 6 grams of L-citrulline can help reduce blood pressure and improve endothelial function. A meta-analysis published in Current Hypertension Reports found that this range was effective in lowering both systolic and diastolic blood pressure in hypertensive individuals. It's important to note that these effects may take a few weeks to become noticeable, so consistent daily supplementation is recommended.

When it comes to managing erectile dysfunction, research has shown that a daily dosage of around 1.5 to 3 grams of L-citrulline can improve erectile function in men with mild to moderate ED. A study published in the journal Urology reported that men who took 1.5 grams of L-citrulline daily experienced significant improvements in erectile hardness compared to those who took a placebo. This dosage is typically taken once daily, and the effects may become more pronounced with continued use.

While these dosages have been found to be effective and generally safe in clinical studies, individual responses to citrulline can vary. Factors such as body weight, overall health, and specific health conditions can influence the optimal dosage. It is always advisable to start with a lower dose to assess tolerance and gradually increase as needed. Additionally, consulting with a healthcare provider before starting citrulline supplementation is recommended, especially for individuals with underlying health conditions or those taking other medications.

In summary, the recommended dosage of citrulline varies depending on the intended use:

• For exercise performance: 6 to 8 grams of citrulline malate 30 to 60 minutes before exercise.
• For cardiovascular health: 3 to 6 grams of L-citrulline daily.
• For erectile dysfunction: 1.5 to 3 grams of L-citrulline daily.

These guidelines provide a general framework, but individual needs and responses may vary, so it is important to adjust accordingly and seek professional advice when necessary.

Citrulline is generally well-tolerated by most individuals, and serious side effects are rare. The amino acid is naturally found in certain foods, such as watermelon, and is produced endogenously in the body. Nonetheless, like any supplement, citrulline can cause side effects in some people, particularly at higher doses or when taken without proper guidance.

One of the most commonly reported side effects of citrulline supplementation is gastrointestinal discomfort. This can include symptoms such as bloating, gas, and diarrhea. These effects are typically mild and may diminish as the body adjusts to the supplement. To minimize the risk of gastrointestinal issues, it is advisable to start with a lower dose and gradually increase it, allowing the digestive system to acclimate. Taking citrulline with food can also help reduce these symptoms.

Another potential side effect is a drop in blood pressure. While the ability of citrulline to lower blood pressure can be beneficial for individuals with hypertension, it may cause dizziness or lightheadedness in those with normal or already low blood pressure. This effect is due to citrulline's role in increasing nitric oxide production, which leads to vasodilation and improved blood flow. Individuals who are prone to low blood pressure should monitor their blood pressure regularly and consult with a healthcare provider before starting citrulline supplementation.

In rare cases, some individuals may experience allergic reactions to citrulline supplements. Symptoms of an allergic reaction can include itching, rash, swelling, and difficulty breathing. If any of these symptoms occur, it is important to discontinue use immediately and seek medical attention. Allergic reactions are uncommon, but they can occur, particularly in individuals with sensitivities to amino acid supplements.

Overall, citrulline is considered safe for most people when taken at recommended dosages. However, it is essential to be aware of potential side effects and to monitor the body's response to the supplement. If any adverse effects are experienced, reducing the dosage or discontinuing use may be necessary. As with any supplement, consulting with a healthcare provider before beginning citrulline supplementation is advisable, especially for individuals with pre-existing health conditions or those taking other medications.

In summary, the main side effects of citrulline include gastrointestinal discomfort, potential drops in blood pressure, and rare allergic reactions. These effects are usually mild and can often be managed by adjusting the dosage or taking the supplement with food. Always consult with a healthcare provider to ensure the safe and effective use of citrulline.

While citrulline is generally considered safe for most people, certain individuals should exercise caution or avoid taking citrulline supplements altogether. Understanding who should not take citrulline can help prevent potential adverse effects and ensure safe usage.

Firstly, individuals with low blood pressure or those prone to hypotension should be cautious with citrulline supplementation. Citrulline increases nitric oxide production, leading to vasodilation and lowered blood pressure. For those who already have low blood pressure, this effect can exacerbate symptoms such as dizziness, lightheadedness, and fainting. Monitoring blood pressure regularly and consulting with a healthcare provider before starting citrulline is crucial for these individuals.

Secondly, people taking medications that affect blood pressure or blood flow should consult with their healthcare provider before using citrulline. This includes individuals on antihypertensive medications, nitrates, or phosphodiesterase inhibitors (such as sildenafil for erectile dysfunction). Citrulline can enhance the effects of these medications, potentially leading to dangerously low blood pressure or other cardiovascular issues. A healthcare provider can help determine if citrulline is safe to use in conjunction with these medications and may adjust dosages accordingly.

Additionally, individuals with certain medical conditions should avoid citrulline or use it under strict medical supervision. For example, those with kidney disorders may need to be cautious, as citrulline is metabolized in the kidneys. High doses of citrulline could potentially strain kidney function or interfere with existing treatments. Similarly, people with liver disorders should be careful, as the liver plays a role in amino acid metabolism, and any disruption could affect overall health.

Pregnant or breastfeeding women should also avoid citrulline supplements unless specifically advised by a healthcare provider. While citrulline is naturally present in some foods, the safety of high-dose supplementation during pregnancy or lactation has not been well studied. It is important to err on the side of caution and consult with a healthcare professional to ensure the safety of both mother and child.

Lastly, individuals with known allergies or sensitivities to amino acid supplements should avoid citrulline to prevent allergic reactions. Symptoms of an allergic reaction can include itching, rash, swelling, and difficulty breathing. If any of these symptoms occur, it is essential to discontinue use immediately and seek medical attention.

In summary, individuals with low blood pressure, those taking certain medications, people with kidney or liver disorders, pregnant or breastfeeding women, and those with known allergies to amino acids should avoid citrulline or consult with a healthcare provider before use. This precautionary approach helps ensure safe and effective supplementation, tailored to individual health needs and conditions.

Yes, citrulline supplements can interact with certain medications, and it is essential to be aware of these potential interactions to ensure safe use. Citrulline primarily affects the body's nitric oxide production and vasodilation processes, which can have implications for medications that influence blood pressure, blood flow, and cardiovascular function. Here are some key medications that may interact with citrulline supplements:

1. Antihypertensive Medications: Citrulline can lower blood pressure by increasing nitric oxide production and promoting vasodilation. For individuals taking antihypertensive medications, such as ACE inhibitors, beta-blockers, calcium channel blockers, or diuretics, the combined effect may lead to an excessive drop in blood pressure. This can result in symptoms such as dizziness, lightheadedness, and fainting. It is crucial for individuals on these medications to consult with their healthcare provider before starting citrulline supplements to monitor and adjust dosages as needed.
2. Nitrates: Nitrates, such as nitroglycerin or isosorbide dinitrate, are often prescribed for angina (chest pain) and other heart conditions. These medications work by dilating blood vessels, similar to the effect of increased nitric oxide from citrulline. Combining nitrates with citrulline can amplify the vasodilatory effect, potentially leading to dangerously low blood pressure. Individuals taking nitrate medications should avoid citrulline supplements unless advised otherwise by their healthcare provider.
3. Phosphodiesterase Type 5 (PDE5) Inhibitors: PDE5 inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), are commonly used to treat erectile dysfunction. These medications enhance the effects of nitric oxide, leading to increased blood flow to the penis. When combined with citrulline, there may be an additive effect, resulting in a significant drop in blood pressure. Individuals using PDE5 inhibitors should use citrulline supplements with caution and under medical supervision.
4. Blood Thinners and Anticoagulants: While citrulline is not directly known to interact with blood thinners or anticoagulants, such as warfarin (Coumadin) or aspirin, its effects on blood flow and vessel dilation could theoretically influence coagulation and bleeding risk. Individuals on these medications should consult with their healthcare provider before starting citrulline to ensure it does not interfere with their treatment regimen.
5. Diuretics: Diuretics, also known as water pills, are used to manage conditions such as hypertension, heart failure, and edema by promoting the excretion of excess fluid. The vasodilatory effects of citrulline may enhance the blood pressure-lowering effects of diuretics, potentially leading to hypotension. Close monitoring and consultation with a healthcare provider are recommended for individuals taking diuretics who wish to use citrulline supplements.

In summary, citrulline supplements can interact with antihypertensive medications, nitrates, PDE5 inhibitors, blood thinners, and diuretics. These interactions primarily involve the additive effects on blood pressure and blood flow, which can lead to adverse outcomes if not properly managed. It is essential for individuals taking these medications to consult with their healthcare provider before starting citrulline supplementation to ensure safe and effective use.

Citrulline can be obtained from both dietary sources and supplements, each offering various benefits. While dietary sources may provide additional nutrients and are suitable for general health maintenance, supplements are often preferred for therapeutic purposes due to their concentrated doses.

Dietary Sources

1. Watermelon: Watermelon is one of the richest natural sources of citrulline, particularly in the rind. Consuming watermelon can provide a substantial amount of citrulline along with other beneficial nutrients like vitamins A and C, lycopene, and antioxidants. Studies have shown that the flesh of the watermelon contains lower concentrations of citrulline compared to the rind, so including both parts in your diet can maximize your intake.
2. Cucumbers: Similar to watermelon, cucumbers contain citrulline, though in smaller amounts. They are a refreshing and hydrating food that can be easily incorporated into salads, smoothies, or eaten raw.
3. Pumpkins and Gourds: These vegetables also contain citrulline and can be a part of a healthy diet. Consuming a variety of gourds and squashes can contribute to your overall citrulline intake.
4. Bitter Melon: Although not as commonly consumed, bitter melon is another source of citrulline. It is often used in traditional medicine and can be included in various culinary dishes.

Supplements

For those looking to achieve higher doses of citrulline for specific health benefits, such as enhancing exercise performance or managing blood pressure, supplements are a more practical option. Citrulline supplements are available in various forms:

1. L-Citrulline: This is the pure form of the amino acid and is typically available in powder or capsule form. L-citrulline is effective for increasing plasma arginine levels and promoting nitric oxide production.
2. Citrulline Malate: This form combines citrulline with malic acid, which is believed to aid in energy production and reduce muscle fatigue. Citrulline malate is particularly popular among athletes and those looking to improve exercise performance. A study published in the Journal of Strength and Conditioning Research found that citrulline malate supplementation significantly enhanced performance during high-intensity resistance training.
3. Watermelon Extract: Some supplements use watermelon extract as a natural source of citrulline. These can be a good option for those who prefer a more natural, food-based supplement.

Choosing the Right Supplement

When selecting a citrulline supplement, it is important to look for products that are third-party tested for purity and potency. High-quality supplements should contain minimal additives and fillers and provide clear dosage information. Opt for reputable brands that adhere to Good Manufacturing Practices (GMP) to ensure the safety and efficacy of the product.

In conclusion, while dietary sources like watermelon, cucumbers, pumpkins, and gourds can provide citrulline along with other nutrients, supplements offer a more concentrated and convenient way to achieve therapeutic doses. Whether you choose dietary sources or supplements, incorporating citrulline into your routine can support various aspects of health, including cardiovascular function, exercise performance, and muscle recovery.

Citrulline is available in several different forms, each offering unique benefits and applications depending on the individual's needs and goals. The primary forms of citrulline include L-citrulline, citrulline malate, and watermelon extract. Understanding the differences between these forms can help you choose the most appropriate one for your specific health objectives.

L-Citrulline

L-citrulline is the pure form of the amino acid and is commonly available as a dietary supplement. It is often found in powder or capsule form. L-citrulline is highly effective at increasing plasma arginine levels, which in turn boosts nitric oxide production. This form is particularly beneficial for those looking to improve cardiovascular health, lower blood pressure, and enhance exercise performance. A study published in the British Journal of Clinical Pharmacology demonstrated that L-citrulline supplementation effectively raises plasma arginine levels and enhances nitric oxide-dependent signaling.

Citrulline Malate

Citrulline malate is a compound that combines citrulline with malic acid. Malic acid is involved in the Krebs cycle, a critical energy production pathway in the body. Citrulline malate is especially popular among athletes and fitness enthusiasts due to its dual benefits: it not only increases nitric oxide production but also helps reduce muscle fatigue and enhance endurance. A study in the Journal of Strength and Conditioning Research found that citrulline malate supplementation significantly improved exercise performance, increasing the number of repetitions during high-intensity resistance training and reducing muscle soreness.

Watermelon Extract

Watermelon extract is another form of citrulline supplement that derives citrulline naturally from watermelon. This form is appealing to those who prefer more natural, food-based supplements. Watermelon extract provides the benefits of citrulline along with other nutrients found in watermelon, such as vitamins A and C and antioxidants like lycopene. While the concentration of citrulline in watermelon extract may be lower compared to pure L-citrulline or citrulline malate supplements, it can still be a valuable addition to a balanced diet and supplement regimen.

Powder vs. Capsules

Citrulline supplements are commonly available in both powder and capsule forms. Each form has its advantages:

1. Powder: Citrulline powder is versatile and can be easily mixed with water, juice, or a pre-workout shake. This form allows for flexible dosing, making it easier to adjust the amount based on individual needs. Powder supplements often come in flavored and unflavored options, catering to personal preferences.
2. Capsules: Citrulline capsules offer convenience and portability, making them ideal for those who prefer a straightforward, no-mix option. Capsules provide precise dosing, ensuring consistent intake with each serving. They are also a good choice for individuals who may not enjoy the taste or texture of powdered supplements.

Choosing the Right Form

When selecting a citrulline supplement, it's essential to consider your specific health goals and preferences. For general cardiovascular health and blood pressure management, L-citrulline may be sufficient. For athletic performance and muscle recovery, citrulline malate could offer additional benefits due to its role in energy production and fatigue reduction. If you prefer a natural approach, watermelon extract provides the benefits of citrulline along with other nutrients.

In summary, citrulline is available in various forms, including L-citrulline, citrulline malate, and watermelon extract, as well as in powder and capsule formats. Each form has unique benefits, and choosing the right one depends on your specific health objectives and personal preferences.

Citrulline itself is a key amino acid with notable health benefits, but its efficacy is often enhanced when combined with other compounds that either support its functions or provide additional synergistic effects. The most significant sub-compound associated with citrulline is malic acid, especially when they are combined to form citrulline malate. This combination is particularly popular in sports nutrition for its dual impact on nitric oxide production and energy metabolism.

Malic Acid

Malic acid is an organic compound that plays an essential role in the Krebs cycle, a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats, and proteins into carbon dioxide and water. When citrulline is combined with malic acid to form citrulline malate, the benefits are twofold:

1. Enhanced Nitric Oxide Production: Citrulline malate increases plasma arginine levels, which then boosts nitric oxide production. Nitric oxide is crucial for vasodilation, improving blood flow, and enhancing the delivery of oxygen and nutrients to muscles during exercise.
2. Improved Energy Production: Malic acid contributes to the Krebs cycle, helping to produce ATP, the primary energy carrier in cells. This leads to better energy production and reduced muscle fatigue during and after intense exercise.

A study published in the Journal of Strength and Conditioning Research found that citrulline malate supplementation significantly improved exercise performance, increased repetitions during high-intensity resistance training, and reduced muscle soreness. This demonstrates the added benefits of malic acid when combined with citrulline.

Arginine

While not a sub-compound of citrulline, arginine is closely related in terms of metabolic pathways and physiological effects. Citrulline is converted into arginine in the kidneys, making it a precursor to arginine. Arginine is directly involved in nitric oxide synthesis, which is critical for vasodilation and improved blood flow. Supplementing with citrulline can be more effective than taking arginine alone because citrulline bypasses the liver's first-pass metabolism, resulting in higher plasma arginine levels. This makes citrulline a more efficient way to increase arginine levels and, subsequently, nitric oxide production.

Synergistic Ingredients

In some formulations, citrulline is combined with other ingredients to enhance its efficacy further. These synergistic combinations can include:

1. Glutathione: Glutathione is a powerful antioxidant that can protect nitric oxide from oxidative degradation, enhancing and prolonging its effects. A study in the Journal of the International Society of Sports Nutrition found that combining citrulline with glutathione significantly increased nitric oxide levels compared to citrulline alone.
2. Branched-Chain Amino Acids (BCAAs): BCAAs, which include leucine, isoleucine, and valine, are often combined with citrulline to support muscle protein synthesis and recovery. This combination can be particularly beneficial for athletes engaged in intense training.

Watermelon Extract

As a natural source of citrulline, watermelon extract can provide additional nutrients like vitamins A and C, lycopene, and antioxidants. While the concentration of citrulline might be lower in watermelon extract compared to pure supplements, the presence of these additional compounds can offer complementary health benefits.

In conclusion, while citrulline itself is highly effective, its efficacy can be enhanced when combined with certain sub-compounds and synergistic ingredients. Malic acid in citrulline malate, arginine, glutathione, and BCAAs all contribute to the overall benefits of citrulline supplementation, providing improved nitric oxide production, better energy metabolism, and enhanced muscle recovery.

Citrulline is recognized by several names and abbreviations, and it's often referred to in various forms depending on its usage and combination with other compounds. Here are some of the common names, abbreviations, chemical compounds, and ingredients associated with citrulline:

Common Names and Abbreviations

1. L-Citrulline: This is the most common form of citrulline found in supplements. The "L" prefix indicates the specific isomer of citrulline that is used by the body.
2. Citrulline Malate: This form combines citrulline with malic acid. It is often abbreviated as CM and is popular in sports supplements due to its dual benefits of enhancing nitric oxide production and energy metabolism.
3. Citrulline DL-Malate: This is another form of citrulline malate, where "DL" indicates a racemic mixture of malic acid. It is sometimes used in supplements, though citrulline malate is more common.
4. Watermelon Extract: As a natural source of citrulline, supplements labeled as watermelon extract may contain citrulline along with other beneficial compounds found in watermelon.

Chemical Compounds and Ingredients

1. Citrulline: This is the simplest form of the amino acid, often used in scientific contexts.
2. Malic Acid (Malate): When combined with citrulline to form citrulline malate, malic acid plays a crucial role in the Krebs cycle, enhancing energy production and reducing muscle fatigue.
3. Arginine: While not a form of citrulline, arginine is a closely related amino acid. Citrulline is converted into arginine in the body, which then boosts nitric oxide production.
4. Glutathione: Sometimes combined with citrulline in supplements to protect nitric oxide from oxidative degradation, enhancing its effectiveness.

Common Misspellings and Variations

1. Citruline: A common misspelling that omits one "l".
2. Citruilline: Another misspelling with the "u" and "i" transposed.
3. L-Citruline: A variation that combines the misspelling with the common abbreviation "L".

Other Names and Related Terms

1. Citrulline Amino Acid: Sometimes referred to in the context of its role as an amino acid.
2. Citrulline-Arginine Pathway: Highlighting its role in the conversion to arginine and subsequent nitric oxide production.
3. Urea Cycle Intermediate: Refers to its role in the urea cycle, helping to detoxify ammonia in the body.

In summary, citrulline is known by various names and forms, including L-citrulline, citrulline malate, and watermelon extract. It is frequently associated with malic acid (malate) and arginine due to their interconnected roles in nitric oxide production and energy metabolism. Common misspellings like "citruline" and "citruilline" are also seen, but the correct terminology ensures clear communication and understanding of this beneficial amino acid.

When selecting a citrulline supplement, it's essential to scrutinize the product label to ensure you are choosing a high-quality and effective product. Here are several key factors to consider when evaluating a citrulline supplement:

1. Form of Citrulline

The form of citrulline is crucial as it affects the supplement's efficacy and intended use:

• L-Citrulline: Look for this form if your primary goal is to increase nitric oxide production and improve cardiovascular health.
• Citrulline Malate: This form is preferable for enhancing exercise performance and reducing muscle fatigue. Ensure the label specifies the ratio of citrulline to malic acid, commonly 2:1.

2. Dosage

Check the dosage per serving to ensure it aligns with the recommended amounts for your specific needs:

• Exercise Performance: 6 to 8 grams of citrulline malate taken 30 to 60 minutes before exercise.
• Cardiovascular Health: 3 to 6 grams of L-citrulline daily.
• Erectile Dysfunction: 1.5 to 3 grams of L-citrulline daily.

3. Purity and Potency

High-quality supplements should provide information on the purity and potency of the ingredients:

• Third-Party Testing: Look for supplements that have been third-party tested for purity and potency. This ensures that the product contains the stated amount of citrulline and is free from contaminants.
• Certifications: Certifications such as NSF Certified for Sport, Informed-Sport, or USP Verified indicate that the product meets high standards for quality and safety.

4. Ingredients List

Review the ingredients list to ensure there are no unnecessary fillers, additives, or artificial ingredients:

• Active Ingredients: The label should clearly list citrulline or citrulline malate as the primary active ingredient.
• Inactive Ingredients: Avoid products with excessive fillers, artificial colors, flavors, or preservatives. A minimal number of inactive ingredients is preferable.

5. Brand Reputation

Choose supplements from reputable brands known for their quality and transparency:

• Company History: Established companies with a history of producing high-quality supplements are generally more reliable.
• Customer Reviews: Reading customer reviews can provide insights into the product's effectiveness and any potential issues.

6. Manufacturing Standards

Ensure the supplement is manufactured according to high standards:

• Good Manufacturing Practices (GMP): Look for a GMP certification, which indicates that the product is manufactured in a facility that adheres to strict quality control standards.
• Allergen Information: Check for potential allergens if you have any sensitivities. The label should indicate whether the product is free from common allergens like gluten, soy, dairy, and nuts.

7. Expiration Date and Storage Information

Verify the expiration date to ensure freshness and potency:

• Expiration Date: Choose a product with a clear and reasonable expiration date to ensure it remains effective.
• Storage Instructions: Follow any storage instructions on the label to maintain the supplement's quality.

8. Serving Size and Number of Servings

Consider the serving size and the total number of servings per container:

• Value for Money: Calculate the cost per serving to determine if the product offers good value for your investment.

In summary, when selecting a citrulline supplement, look for the specific form of citrulline, appropriate dosage, purity and potency through third-party testing, minimal inactive ingredients, reputable brands, GMP certification, clear expiration date, and value for money. By carefully evaluating these factors, you can ensure that you choose a high-quality citrulline supplement that meets your health and performance needs.

The information provided on this website, including any text, images, or other material contained within, is for informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. This page was created by the SuppCo editiorial team, with AI summarization tools, including data from but not limited to following studies:

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25. A. Maharaj, Stephen M. Fischer, Katherine N. Dillon, Yejin Kang, Mauricio A. Martinez, A. Figueroa (2022). Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients, 14, . Link: 10.3390/nu14204396
26. P. Alsop, D. Hauton (2016). Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure. European Journal of Applied Physiology, 116, 1651 - 1661. Link: 10.1007/s00421-016-3418-7
27. M. Morita, Toshio Hayashi, Masayuki Ochiai, Morihiko Maeda, Tomoe Yamaguchi, K. Ina, M. Kuzuya (2014). Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability.. Biochemical and biophysical research communications, 454 1,
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28. Adam M. Gonzalez, E. Trexler (2020). Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature.. Journal of Strength and Conditioning Research, , . Link: 10.1519/JSC.0000000000003426
29. T. Churchward-Venne, L. Cotie, M. MacDonald, C. Mitchell, T. Prior, S. Baker, Stuart M Phillips (2014). Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise.. American journal of physiology. Endocrinology and metabolism, 307 1,
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30. Il-Young Kim, Scott E Schutzler, Amy M. Schrader, H. Spencer, G. Azhar, N. Deutz, R. Wolfe (2015). Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.. American journal of physiology. Endocrinology and metabolism, 309 11,
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31. Bahareh Barkhidarian, M. Khorshidi, S. Shab-Bidar, Baran Hashemi (2019). Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis. Avicenna Journal of Phytomedicine, 9, 10 - 20. Link: 10.22038/AJP.2018.11590
32. A. Figueroa, Stacey Alvarez‐Alvarado, Salvador J. Jaime, R. Kalfon (2016). l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men.. The British journal of nutrition, 116 2,
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33. A. Maharaj, Stephen M. Fischer, Katherine N. Dillon, Yejin Kang, Mauricio A. Martinez, A. Figueroa (2022). Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients, 14, . Link: 10.3390/nu14204396
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37. A. Figueroa, Julian A Trivino, M. Sanchez-Gonzalez, F. Vicil (2010). Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men.. American journal of hypertension, 23 1,
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38. Sepideh Mahboobi, C. Tsang, S. Rezaei, S. Jafarnejad (2018). Effect of l-citrulline supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. Journal of Human Hypertension, 33, 10-21. Link: 10.1038/s41371-018-0108-4
39. Huan-Huan Yang, Xinli Li, Weiguo Zhang, A. Figueroa, Li-Hua Chen, L. Qin (2019). Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials. Nutrition & Metabolism, 16, . Link: 10.1186/s12986-019-0415-y
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41. Adam M. Gonzalez, Robert W. Spitz, J. Ghigiarelli, K. Sell, G. Mangine (2017). Acute Effect of Citrulline Malate Supplementation on Upper-Body Resistance Exercise Performance in Recreationally Resistance-Trained Men. Journal of Strength and Conditioning Research, 32, 3088–3094. Link: 10.1519/JSC.0000000000002373
42. Tyler M Farney, Matthew V. Bliss, C. Hearon, D. A. Salazar (2017). The Effect of Citrulline Malate Supplementation On Muscle Fatigue Among Healthy Participants.. Journal of Strength and Conditioning Research, , . Link: 10.1519/JSC.0000000000002356
43. Alyssa N Fick, Robert J. Kowalsky, Matthew S. Stone, C. Hearon, Tyler M Farney (2021). Acute and Chronic Citrulline Malate Supplementation on Muscle Contractile Properties and Fatigue Rate of the Quadriceps.. International journal of sport nutrition and exercise metabolism, ,
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44. I-Fan Chen, Huey-june Wu, Chung-Yu Chen, Kuei-Ming Chou, Chen-Kang Chang (2016). Branched-chain amino acids, arginine, citrulline alleviate central fatigue after 3 simulated matches in taekwondo athletes: a randomized controlled trial. Journal of the International Society of Sports Nutrition, 13, . Link: 10.1186/s12970-016-0140-0
45. E. Bezuglov, R. Morgans, A. Lazarev, E. Kalinin, M. Butovsky, Evgeny Savin, Eduard Tzgoev, B. Pirmakhanov, A. Emanov, A. Zholinsky, O. Talibov (2022). The Effect of a Single Dose of Citrulline on the Physical Performance of Soccer-Specific Exercise in Adult Elite Soccer Players (A Pilot Randomized Double-Blind Trial). Nutrients, 14, . Link: 10.3390/nu14235036
46. F. T. Vårvik, T. Bjørnsen, Adam M. Gonzalez (2021). 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, ,
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49. Takashi Suzuki, M. Morita, Yoshinori Kobayashi, A. Kamimura (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, . Link: 10.1186/s12970-016-0117-z
50. J. Pérez-Guisado, P. Jakeman (2010). Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness. Journal of Strength and Conditioning Research, 24, 1215-1222. Link: 10.1519/JSC.0b013e3181cb28e0
51. H. Rhim, Sung Jong Kim, Jewel Park, K. Jang (2020). 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, 9, 553 - 561. Link: 10.1016/j.jshs.2020.02.003
52. Alyssa N Fick, Robert J. Kowalsky, Matthew S. Stone, C. Hearon, Tyler M Farney (2021). Acute and Chronic Citrulline Malate Supplementation on Muscle Contractile Properties and Fatigue Rate of the Quadriceps.. International journal of sport nutrition and exercise metabolism, ,
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54. Ascensión Martínez-Sánchez, F. Alacid, J. Rubio-Arias, B. Fernández-Lobato, D. Ramos-Campo, E. Aguayo (2017). Consumption of Watermelon Juice Enriched in l-Citrulline and Pomegranate Ellagitannins Enhanced Metabolism during Physical Exercise.. Journal of agricultural and food chemistry, 65 22,
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55. M. P. Tarazona-Díaz, F. Alacid, María Carrasco, Ignacio Martínez, E. Aguayo (2013). Watermelon juice: potential functional drink for sore muscle relief in athletes.. Journal of agricultural and food chemistry, 61 31,
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56. D. K. da Silva, J. L. Jacinto, W. B. de Andrade, M. C. Roveratti, J. M. Estoche, M. C. W. Balvedi, Douglas B. de Oliveira, R. D. da Silva, A. Aguiar (2017). Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult Men. Nutrients, 9, . Link: 10.3390/nu9101132
57. A. Chappell, Daniel M Allwood, T. Simper (2018). Citrulline Malate Fails to Improve German Volume Training Performance in Healthy Young Men and Women. Journal of Dietary Supplements, 17, 249 - 260. Link: 10.1080/19390211.2018.1513433
58. Ascensión Martínez-Sánchez, D. Ramos-Campo, B. Fernández-Lobato, J. Rubio-Arias, F. Alacid, E. Aguayo (2017). Biochemical, physiological, and performance response of a functional watermelon juice enriched in L-citrulline during a half-marathon race. Food & Nutrition Research, 61, . Link: 10.1080/16546628.2017.1330098
59. A. Chappell, Daniel M Allwood, R. Johns, Samantha Brown, K. Sultana, Annie Anand, T. Simper (2018). Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. Journal of the International Society of Sports Nutrition, 15, . Link: 10.1186/s12970-018-0245-8
60. J. Pérez-Guisado, P. Jakeman (2010). Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness. Journal of Strength and Conditioning Research, 24, 1215-1222. Link: 10.1519/JSC.0b013e3181cb28e0
61. Victoria A Uyanga, Hongchao Jiao, Jingpeng Zhao, Xiaojuan Wang, Hai Lin (2020). Dietary L-citrulline supplementation modulates nitric oxide synthesis and anti-oxidant status of laying hens during summer season. Journal of Animal Science and Biotechnology, , . Link: 10.1186/s40104-020-00507-5
62. E. Schwedhelm, R. Maas, R. Freese, D. Jung, Z. Lukács, A. Jambrecina, W. Spickler, F. Schulze, R. Böger (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.. British journal of clinical pharmacology, 65 1,
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63. Sarah K. McKinley-Barnard, Thomas L. Andre, M. Morita, D. Willoughby (2015). Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. Journal of the International Society of Sports Nutrition, 12, . Link: 10.1186/s12970-015-0086-7
64. S. Bailey, Jamie R. Blackwell, T. Lord, A. Vanhatalo, P. Winyard, A. Jones (2015). l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans.. Journal of applied physiology, 119 4,
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65. F. Holguin, H. Grasemann, Sunita Sharma, D. Winnica, Karen Wasil, V. Smith, M. Cruse, N. Perez, E. Coleman, T. Scialla, L. Que (2019). L-citrulline as add-on therapy to increase nitric oxide, and to improve asthma control in obese asthmatics.. JCI insight, , . Link: 10.1172/jci.insight.131733
66. Il-Young Kim, Scott E Schutzler, Amy M. Schrader, H. Spencer, G. Azhar, N. Deutz, R. Wolfe (2015). Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.. American journal of physiology. Endocrinology and metabolism, 309 11,
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67. A. Theodorou, Panagiotis T Zinelis, Vassiliki J Malliou, P. Chatzinikolaou, N. Margaritelis, D. Mandalidis, N. Geladas, V. Paschalis (2021). Acute L-Citrulline Supplementation Increases Nitric Oxide Bioavailability but Not Inspiratory Muscle Oxygenation and Respiratory Performance. Nutrients, 13, . Link: 10.3390/nu13103311
68. D. Heck (2021). Citrulline Recycling Supports Nitric Oxide Biosynthesis in Mouse PAM212 Keratinocytes. The FASEB Journal, 35, . Link: 10.1096/FASEBJ.2021.35.S1.04804
69. V. Uyanga, Minghui Wang, Tian Tong, Jingpeng Zhao, Xiaojuan Wang, H. Jiao, O. Onagbesan, Hai Lin (2021). L-Citrulline Influences the Body Temperature, Heat Shock Response and Nitric Oxide Regeneration of Broilers Under Thermoneutral and Heat Stress Condition. Frontiers in Physiology, 12, . Link: 10.3389/fphys.2021.671691
70. A. El-Hattab, L. Emrick, W. Craigen, F. Scaglia (2012). Citrulline and arginine utility in treating nitric oxide deficiency in mitochondrial disorders.. Molecular genetics and metabolism, 107 3,
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72. E. Schwedhelm, R. Maas, R. Freese, D. Jung, Z. Lukács, A. Jambrecina, W. Spickler, F. Schulze, R. Böger (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.. British journal of clinical pharmacology, 65 1,
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73. S. Azizi, M. Ebrahimi‐Mameghani, M. Mobasseri, N. Karamzad, Reza Mahdavi (2020). Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial.. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association, , . Link: 10.1111/jhn.12792
74. D. Tsikas, N. Maassen, Antonie Thorns, Armin Finkel, Moritz Lützow, Magdalena Aleksandra Röhrig, Larissa Sarah Blau, Laurianne Dimina, F. Mariotti, Bibiana Beckmann, V. Shushakov, Mirja Jantz (2022). Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise. International Journal of Molecular Sciences, 23, . Link: 10.3390/ijms231810649
75. Takashi Suzuki, M. Morita, Yoshinori Kobayashi, A. Kamimura (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, . Link: 10.1186/s12970-016-0117-z
76. Adam M. Gonzalez, E. Trexler (2020). Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature.. Journal of Strength and Conditioning Research, , . Link: 10.1519/JSC.0000000000003426
77. Paul S. Hwang, Flor E. Morales Marroquín, Josh Gann, Thomas L. Andre, Sarah K. McKinley-Barnard, Caelin S. Kim, M. Morita, D. Willoughby (2018). Eight weeks of resistance training in conjunction with glutathione and L-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained males. Journal of the International Society of Sports Nutrition, 15, . Link: 10.1186/s12970-018-0235-x
78. R. Thibault, L. Flet, F. Vavasseur, M. Lemerle, V. Ferchaud‐Roucher, D. Picot, D. Darmaun (2011). Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study.. Clinical nutrition, 30 6,
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79. S. Bailey, Jamie R. Blackwell, T. Lord, A. Vanhatalo, P. Winyard, A. Jones (2015). l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans.. Journal of applied physiology, 119 4,
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80. E. Trexler, Dale S. Keith, T. Schwartz, E. Ryan, Lee Stoner, A. Persky, A. Smith‐Ryan (2019). 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, , . Link: 10.1519/JSC.0000000000003286
81. Aitor Viribay, Julen Fernández-Landa, Arkaitz Castañeda-Babarro, P. S. Collado, Diego Fernández-Lázaro, J. Mielgo-Ayuso (2022). Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis. Nutrients, 14, . Link: 10.3390/nu14173479
82. F. T. Vårvik, T. Bjørnsen, Adam M. Gonzalez (2021). 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, ,
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