L-Citrulline: Uses and Risks

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L-citrulline supplementation offers several potential benefits, particularly in enhancing exercise performance, supporting fetal growth, and improving metabolic health. However, its effects can vary based on the population and specific conditions, and there are instances where it may not provide the expected benefits. While generally safe, further research is needed to fully understand the long-term risks and establish optimal dosing guidelines.

L-citrulline, a non-essential amino acid, has garnered attention for its potential health benefits and applications in various physiological conditions. It is a precursor to L-arginine, which plays a crucial role in nitric oxide (NO) production, a key molecule in vascular health. This article explores the uses and potential risks associated with L-citrulline supplementation based on recent research findings.

Uses of L-Citrulline

Enhancing Exercise Performance

L-citrulline has been shown to improve exercise performance by enhancing blood flow and reducing muscle fatigue. A study demonstrated that oral L-citrulline supplementation improved cycling time trial performance in trained men, reducing completion time and improving subjective feelings of muscle fatigue and concentration10. Another study found that L-citrulline intake before exercise preserved splanchnic perfusion and attenuated intestinal injury, suggesting benefits for athletes1.

Supporting Fetal Growth

In a model of intrauterine growth restriction (IUGR) induced by maternal dietary protein restriction, L-citrulline supplementation enhanced fetal growth and protein synthesis. This effect was attributed to increased nitric oxide production and improved placental blood flow2.

Cardiovascular Health

L-citrulline has been investigated for its potential to lower blood pressure and improve vascular function. While one study found that short-term L-citrulline supplementation did not affect blood pressure or arterial stiffness in older males3, another study reported that L-citrulline reduced brachial and aortic blood pressure responses to a cold pressor test in young men8. These mixed results suggest that the effects of L-citrulline on cardiovascular health may vary based on the population and specific conditions.

Metabolic Health

L-citrulline supplementation has shown promise in improving glucose homeostasis and lipid profiles in patients with type 2 diabetes. A study reported significant reductions in serum insulin, glucose, HbA1c, and inflammatory markers in overweight and obese patients with type 2 diabetes following L-citrulline supplementation6. Additionally, another study found that L-citrulline supplementation in critically ill patients reduced fasting blood sugar, total cholesterol, and LDL-C levels, and improved survival without mechanical ventilation7.

Risks of L-Citrulline

Potential Negative Effects on Exercise Performance

Contrary to the expected benefits, one study found that L-citrulline supplementation reduced treadmill time to exhaustion and altered insulin response during high-intensity exercise in healthy individuals. This suggests that L-citrulline may not always enhance exercise performance and could potentially impair it under certain conditions4.

Lack of Effect on Respiratory Performance

In older adults, short-term L-citrulline supplementation did not affect inspiratory muscle oxygenation or respiratory performance, indicating that its benefits may not extend to all aspects of physical function9.

Safety and Tolerability

Overall, L-citrulline is considered safe and well-tolerated. However, the long-term effects and safety profile of high-dose supplementation require further investigation. Most studies have reported no significant adverse effects, but individual responses can vary, and more research is needed to establish comprehensive safety guidelines5.