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Is Citrulline a Vasodilator?

Citrulline is indeed a vasodilator, primarily through its conversion to L-arginine and subsequent increase in nitric oxide production. This amino acid has shown potential in improving blood flow and reducing blood pressure.

Citrulline, a non-essential amino acid, has captured the attention of researchers and health enthusiasts alike. Its ability to widen blood vessels and enhance circulation has made it a subject of intense study. We investigate the science behind citrulline’s vasodilatory effects and its potential benefits.

How Citrulline Works in the Body

Citrulline’s journey in the body is fascinating. Once ingested, it doesn’t directly cause vasodilation. Instead, it undergoes a transformation process that ultimately leads to increased blood flow.

The body converts citrulline into another amino acid called L-arginine. This conversion happens in the kidneys and other tissues. L-arginine then serves as a precursor for nitric oxide synthesis. Nitric oxide is the real star of the show when it comes to vasodilation.

Nitric oxide is a powerful molecule that relaxes the smooth muscles in blood vessel walls. When these muscles relax, the blood vessels widen, allowing for increased blood flow. This process is what we call vasodilation.

The conversion of citrulline to L-arginine involves two enzymes: argininosuccinate synthase and argininosuccinate lyase. Once L-arginine is produced, it becomes a substrate for endothelial nitric oxide synthase (eNOS). This enzyme is responsible for producing nitric oxide.

Interestingly, taking citrulline supplements may be more effective at raising L-arginine levels than taking L-arginine supplements directly. This is because citrulline bypasses the liver’s first-pass metabolism, allowing more of it to reach the bloodstream and be converted to L-arginine.

Animal Studies Support Citrulline’s Effects

Research on animals has provided compelling evidence for citrulline’s vasodilatory effects. These studies offer valuable insights into how citrulline might work in humans.

One study focused on rats and examined how oral citrulline administration affected blood flow. The researchers used Evans blue dye (EBD) to measure blood flow in skeletal muscles. They found that citrulline increased EBD levels in the muscles, indicating enhanced blood flow. This effect was observed in both healthy rats and those with type 1 diabetes.

Another intriguing area of research involves hypertension models. In rats with spontaneous hypertension, L-citrulline supplementation showed promising results. It prevented the development of high blood pressure by increasing the ratio of L-arginine to asymmetrical dimethylarginine (ADMA). This suggests that citrulline can boost nitric oxide production and improve the function of the endothelium, the inner lining of blood vessels.

These animal studies provide a strong foundation for understanding citrulline’s potential in humans. Nevertheless it’s essential to remember that results in animals don’t always translate directly to humans. That’s why human studies are crucial for confirming these effects.

Human Studies Reveal Promising Results

Human studies have added weight to the evidence supporting citrulline’s vasodilatory effects. These studies have looked at various aspects of cardiovascular health and performance.

One of the most significant findings comes from a meta-analysis of randomized clinical trials. This analysis found that L-citrulline supplementation led to notable reductions in blood pressure. On average, systolic blood pressure decreased by 4.10 mm Hg, while diastolic blood pressure dropped by 2.08 mm Hg. Interestingly, the effect on diastolic blood pressure was more pronounced in studies using doses of 6 grams per day or more.

Another essential measure of vasodilation is flow-mediated dilation (FMD). This test assesses how well the endothelium causes blood vessels to dilate in response to increased blood flow. A study presented at a nutrition conference compared citrulline malate with another supplement called Nitrosigine. Both supplements significantly increased FMD compared to a placebo. Citrulline malate increased FMD by 34%, while the placebo showed a 2% decrease. This suggests that citrulline can enhance endothelial-dependent vasodilation.

Citrulline’s Impact on Athletic Performance

The vasodilatory effects of citrulline extend beyond just cardiovascular health. They also have implications for athletic performance. By increasing blood flow to working muscles, citrulline may enhance oxygen delivery and nutrient transport. This could potentially improve endurance and reduce muscle soreness.

One study looked at the effects of citrulline malate on weight training performance. Men who took a citrulline malate supplement were able to perform 53% more repetitions in a weight training exercise compared to those who took a placebo. This significant improvement suggests that citrulline’s vasodilatory effects may translate to real-world performance benefits.

The increased blood flow to muscles may also help with recovery after exercise. Better circulation could mean faster removal of waste products and delivery of nutrients to tired muscles. Nevertheless more research is needed to fully understand the extent of citrulline’s benefits for athletic recovery.

Limitations and Areas for Further Research

Despite the promising findings, it’s essential to acknowledge that not all studies have shown consistent results. Some research has found no significant differences in vascular responses between citrulline supplements and placebos.

For example, a study involving healthy young men found no significant differences in vascular responses between a combined nitrate-citrulline supplement and a placebo during post-ischemia conditions. This suggests that the vasodilatory effects of citrulline may be limited by certain physiological factors. These could include vessel compliance (how easily blood vessels can expand and contract) and baseline endothelial function.

It’s also worth noting that many of the existing studies have limitations. Many have small sample sizes and short intervention durations. This makes it difficult to draw definitive conclusions about the long-term effects of citrulline supplementation.

Larger, double-blind clinical trials are needed to clarify the effects of citrulline on blood pressure and vascular health. These studies should particularly focus on populations with pre-hypertension or hypertension, as they might benefit most from citrulline’s vasodilatory effects.

Potential Benefits Beyond Vasodilation

While this article focuses on citrulline’s role as a vasodilator, it’s worth mentioning that this amino acid may have other health benefits as well. Some research suggests that citrulline might support immune function, help with erectile dysfunction, and even improve cognitive performance. Nevertheless these areas require further study to confirm the benefits and understand the mechanisms involved.

Dosage and Safety Considerations

The optimal dosage of citrulline for vasodilatory effects is not yet firmly established. Nevertheless many studies have used doses ranging from 3 to 6 grams per day. Some athletic performance studies have used higher doses, up to 8 grams per day.

Citrulline appears to be safe for most people when taken in these amounts. Nevertheless as with any supplement, it’s always best to consult with a healthcare provider before starting a new regimen. This is especially essential for people with existing health conditions or those taking medications.

Key Takeaways

  • Citrulline acts as a vasodilator primarily through its conversion to L-arginine and subsequent increase in nitric oxide production.
  • Animal studies have shown promising results in improving blood flow and reducing blood pressure.
  • Human studies have demonstrated citrulline’s potential to lower blood pressure and improve endothelial function.
  • Citrulline may enhance athletic performance by increasing blood flow to muscles.
  • More research is needed to fully understand citrulline’s long-term effects and optimal dosing strategies.


Citrulline has emerged as a promising natural vasodilator. Its ability to increase nitric oxide production through L-arginine conversion makes it an intriguing subject for cardiovascular health and athletic performance research. While the evidence is largely positive, some inconsistencies in results highlight the need for further study. As research continues, we may gain a clearer understanding of how to harness citrulline’s vasodilatory effects for optimal health benefits. For now, citrulline remains an intriguing option for those looking to support their cardiovascular health naturally.


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