Does L-Citrulline Increase Muscle Mass and Performance?

December 9, 2025 •

4 min read

According to a 2018 study in mice, L-citrulline supplementation increased muscle weight, sparking interest in how does L-citrulline increase muscle in humans. This article delves into the evidence and mechanisms behind this popular supplement, from performance enhancement to muscle recovery.

Quick Summary

Research shows L-citrulline supports muscle indirectly by boosting nitric oxide for better blood flow, improving exercise performance, and aiding recovery by reducing fatigue and soreness.

Key Points

Mechanism of Action: L-citrulline boosts nitric oxide, improving blood flow and delivering more nutrients and oxygen to working muscles.
Muscle Protein Synthesis: Research suggests L-citrulline can stimulate muscle protein synthesis, especially under stressed or low-protein conditions.
Reduced Fatigue: By aiding in the clearance of ammonia, L-citrulline helps reduce muscle fatigue and soreness, supporting higher training volume.
Performance Enhancement: Studies show L-citrulline can improve endurance and reduce perceived exertion during high-intensity and anaerobic exercise.
Supplementation Forms: L-citrulline and Citrulline Malate are the two primary forms, with Citrulline Malate often used for its potential energy-boosting malic acid component.
Optimal Dosage: A typical dosage is 6–8 grams of citrulline malate or 3–6 grams of L-citrulline, usually taken before a workout.
Safety: L-citrulline is generally considered safe, but individuals on blood pressure medication or nitrates should consult a doctor due to potential interactions.

The Scientific Reality of L-Citrulline and Muscle Growth

L-citrulline is a non-essential amino acid that has gained significant attention in the fitness and bodybuilding communities. Unlike some amino acids, it is not used to build proteins directly but plays a crucial role in other physiological processes that indirectly support muscle growth and repair. The body produces L-citrulline naturally, and it can also be found in foods like watermelon. The main appeal of L-citrulline as a supplement is its ability to enhance athletic performance and recovery, which are foundational for building muscle mass over time. Understanding the complex biological pathways involved provides a clearer picture of how L-citrulline contributes to muscular development.

The Mechanisms Behind L-Citrulline and Muscle Growth

L-citrulline's positive effects on muscle are primarily a result of its influence on several key bodily systems. Its impact is more about optimizing the conditions for muscle growth rather than being a direct anabolic agent.

Enhanced Nitric Oxide (NO) Production

One of the most well-documented effects of L-citrulline is its role in boosting nitric oxide (NO) levels in the body. When ingested, L-citrulline is converted into L-arginine, which then serves as a substrate for nitric oxide synthase, the enzyme that produces NO. This increased NO production leads to several beneficial effects for muscle function and growth:

Vasodilation: NO is a powerful vasodilator, meaning it causes blood vessels to widen. This improves blood flow to the muscles, delivering more oxygen, nutrients, and anabolic hormones during exercise.
Improved 'Pump': Enhanced blood flow is responsible for the 'muscle pump' sensation experienced during and after training, which is not just an aesthetic effect but also a mechanism for delivering resources vital for repair.
Better Nutrient Delivery: With increased blood flow, muscles receive nutrients like glucose and amino acids more efficiently, fueling strenuous workouts and supporting post-exercise recovery.

Impact on Muscle Protein Synthesis

Research indicates that L-citrulline can also directly influence muscle protein synthesis (MPS), especially under conditions of metabolic stress or malnutrition.

mTOR Pathway Activation: Some studies, particularly those involving animal and in-vitro models, suggest that L-citrulline can stimulate MPS by activating the mTOR (mammalian target of rapamycin) pathway. The mTOR pathway is a key regulator of cell growth and metabolism, including the rate of protein synthesis.
Energy Reallocation: A study published in the Journal of Cachexia, Sarcopenia and Muscle found that under stressful conditions, citrulline increases protein synthesis by reallocating cellular energy towards the protein synthesis machinery, rather than just increasing overall energy production.

Reduction of Muscle Fatigue and Soreness

L-citrulline assists in clearing metabolic byproducts that cause fatigue, allowing for more sustained and intense training sessions.

Ammonia Clearance: L-citrulline plays a role in the urea cycle, which helps remove waste products like ammonia from the body. A buildup of ammonia can contribute to muscle fatigue during intense exercise.
Reduced Muscle Soreness: Several meta-analyses have concluded that citrulline supplementation significantly reduces post-exercise rating of perceived exertion (RPE) and muscle soreness, especially 24 hours after intense training. This improved recovery allows athletes to train more frequently and with greater intensity over time, which is critical for muscle adaptation and growth.

L-Citrulline vs. Citrulline Malate

There are two main forms of citrulline supplements available, each with a different chemical composition and potential benefits. It's important to understand the distinction when choosing a product.

Comparison of L-Citrulline vs. Citrulline Malate


Feature	L-Citrulline (Pure)	Citrulline Malate
Composition	Pure, free-form L-citrulline amino acid.	A compound of L-citrulline and malic acid.
Benefits	Primary benefit is boosting nitric oxide levels for improved blood flow.	Offers blood flow benefits plus potential energy-boosting effects from malate.
Potency	A higher concentration of pure citrulline by weight, as it is not bound to another compound.	The concentration of pure citrulline is lower, with a typical ratio of 1:1 or 2:1 citrulline to malate.
Research	Supported by research demonstrating its efficacy in raising plasma arginine levels more effectively than L-arginine.	Widely used in research for performance, with many studies showing benefits for endurance and strength.

How to Supplement L-Citrulline for Optimal Results

To maximize the benefits of L-citrulline for muscle and performance, proper dosage and timing are key. The ideal approach can depend on your specific fitness goals.

Dosage and Timing Recommendations

Optimal Dose: For performance enhancement, a dose of 6–8 grams of citrulline malate or 3–6 grams of L-citrulline is commonly recommended. Exceeding 10 grams in a single dose may not provide additional benefits.
Timing: To achieve peak plasma arginine levels and maximize the blood flow 'pump' during a workout, take the supplement approximately 60 minutes before your exercise session.

Potential Side Effects and Safety Considerations

L-citrulline is generally considered safe and well-tolerated, even at higher doses. However, as with any supplement, there are some precautions to consider.

Gastrointestinal Discomfort: While less common than with L-arginine, some individuals may experience mild stomach upset or diarrhea, particularly when taking larger doses.
Medication Interactions: L-citrulline can lower blood pressure. Individuals taking medications for high blood pressure or erectile dysfunction (e.g., nitrates) should consult a healthcare provider before use to avoid blood pressure dropping too low.

Conclusion

In conclusion, while L-citrulline is not a direct muscle-building supplement, its effect on increasing nitric oxide, enhancing performance, and reducing fatigue provides powerful indirect support for muscle growth. It is best viewed as an effective performance aid that allows athletes to train harder, recover faster, and create a more anabolic environment for their muscles. By understanding its mechanisms and using it strategically, individuals can effectively incorporate L-citrulline into their regimen to see improvements in muscle development and athletic performance.

For more in-depth scientific analysis on the role of L-citrulline in muscle protein synthesis, review the study published in the Journal of Cachexia, Sarcopenia and Muscle.

Frequently Asked Questions

L-citrulline does not directly build muscle protein like a protein shake. Instead, it supports muscle growth indirectly by improving exercise performance, reducing fatigue, and enhancing blood flow and nutrient delivery to muscles during workouts.

For acute performance benefits, it's often recommended to take L-citrulline about 60 minutes before exercise. For chronic effects like increased plasma arginine, noticeable changes may take a week or more of consistent daily supplementation.

Yes, L-citrulline is often considered more effective than L-arginine for boosting nitric oxide levels. This is because L-citrulline bypasses the liver and is converted to L-arginine in the kidneys, resulting in higher and more sustained plasma arginine levels.

L-citrulline is the pure amino acid. Citrulline malate is a compound of L-citrulline and malic acid. Some believe malate, a Krebs cycle intermediate, offers additional energy-enhancing benefits, but L-citrulline provides a more concentrated dose of the active ingredient.

Yes, studies suggest that L-citrulline supplementation can help reduce delayed onset muscle soreness (DOMS). This is thought to be related to its role in improved blood flow and nutrient delivery, which assists with recovery.

L-citrulline is generally well-tolerated. Some people may experience mild gastrointestinal discomfort, such as stomach upset, especially at higher doses, but this is less common than with L-arginine.

For workout performance, the best time is about one hour before your training session. For general health benefits, it can be taken daily, with or without food.