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Introduction

L-citrulline is a non-essential amino acid that is an important component of the urea cycle in the liver and kidneys, which rids your body of harmful compounds.

The availability of l-citrulline in food is quite rare, with only watermelon having a considerable amount.

Therefore, supplementation has become very common for people wanting to increase their citrulline content in the body above typical levels, especially when considering it would take ~1–1.5 kg of watermelon per day to reach the minimum effective dose (yikes!).

The benefits of l-citrulline largely stem from its effect on increasing l-arginine levels and stimulating nitric oxide metabolism, which direct l-arginine supplementation fails to achieve.

What Does L-Cirtrulline Do?

L-citrulline supplementation is thought to increase l-arginine levels in the blood and represent a potential mechanism to increase nitric oxide synthesis and bioavailability.

Oral l-arginine supplementation itself is largely ineffective at doing this due to the intestinal and liver extraction of l-arginine, as well as reports of gastrointestinal distress at high doses. Specifically, the activity of an enzyme called arginase located within the intestines and liver significantly reduces the bioavailability of oral l-arginine [1].

As l-citrulline is not acted on by this enzyme, and is unaffected by the liver, it can successfully be converted to bioavailable l-arginine in the kidneys [2] [3].

Increasing nitric oxide metabolism is a mechanism in which to improve vasodilation and widen the arteries and veins to lower blood pressure and increase blood flow [4].

This is because nitric oxide relaxes the smooth muscle cells that would otherwise be constricted [5].

L-Citrulline Health Benefits

May Increase Vasodilation

L-citrulline is one of many supplements that has been named as a “vasodilator” that may have benefits for cardiovascular health and athletic performance.

The only difference between l-citrulline and supplements with similar claims is that l-citrulline has actually proven its effect (hooray).

L-citrulline has consistently shown to synthesize nitric oxide by indirectly increasing l-arginine synthesis, which in turn may lead to improved endothelial vasodilator function [6].

Following oral l-citrulline ingestion, circulating l-arginine concentrations peak after ~1-2 hours [7].

Nitric oxide released from the blood vessels initiates a signaling cascade that ultimately increases vasodilation by relaxing smooth muscle cells [8].

L-citrulline has demonstrated to reduce arterial stiffness in healthy and overweight males in just 1-2 weeks [9] [10], and in hypertensive women with hypertension after 6 weeks [11].

Specifically, l-citrulline can reduce blood pressure by up to 15% [12], and this is seen in some healthy populations too [13].

As individuals with impaired cardiovascular systems often see poor nitric oxide production and bioavailability, this could be important to preventing cardiovascular disease [14].

However, improvements to the vasodilation of blood vessels are not always seen [15] [16].

Keep in mind, the current data does not show short-term benefits to a single dose of L-citrulline [17], and supplementation needs to continue for at least a week for the vasodilatory effects to occur [18].

May Prevent Endothelial Damage

L-citrulline supplementation has been investigated as a therapeutic strategy for preserving blood vessel function.

Given, l-citrulline supplementation has shown modest but favorable structural changes in the endothelial structure of certain arteries [19].

The current science also supports the idea that l-citrulline may protect against endothelial dysfunction that are initially cause by poor dietary habits.

For example, l-citrulline may reduce the amount of fat in the blood of animals that are fed a typical western diet (high fat/high sugar) [20].

However, it is obviously crucial to understand that l-citrulline is in no way a supplement that can reverse the effects of a bad diet.

May Improve Endurance Capacity

Increased levels of nitric oxide has been associated with increased mitochondrial biogenesis (mitochondrial protein synthesis) by activating some transcriptional coregulators such as PGC1-α [21].

Mechanistically, high levels of nitric oxide hinder the normal functioning of the mitochondria, which in turn causes a build-up of energy stress within the cells that may cause the body to adapt by upregulating the amount of mitochondria [22].

At least in animal studies, supplementing with l-citrulline (250mg per kg bodyweight) for 2 weeks has resulted in elevations in PGC1-α and mitochondrial levels. Importantly, this has also led to measurable improvements in exercise performance as measured by a “time to exhaustion” test [23].

Specifically, endurance athletes taking citrulline were able to cycle for ~10% longer before they reached the point of exhaustion [24].

Similar to the effects on vasodilation, l-citrulline does not improve endurance exercise performance from a single dose and it needs to be taken for prolonged periods to see the benefits [25].

How To Take L-Citrulline?

Based on current research, a recommended dose of 3-6 grams per day of L-citrulline is recommended.

For improvements in blood pressure a lower dose will be adequate (~3 grams), however for performance-enhancing effects it is likely that a higher dose is required (~6 grams).

L-Citrulline Safety And Side Effects

L-citrulline is generally a well-tolerated supplement for healthy individuals.

In particular, reviews state that we can tolerate up to 15 grams of l-citrulline per day on average [26].

This is backed by a few different studies where 15 grams of L-citrulline has not shown any negative side effects [27].

However, there do not seem to be any further benefits of supplementing beyond 10 grams of l-citrulline per day. Even doses as low as 3 grams per day have been shown to be very effective [28].

Conclusion

L-citrulline is a non-essential amino acid that has some important roles within human metabolism.

Due to its ability to convert into a bioavailable form of l-arginine, many studies have shown it can increase vasodilation, prevent endothelial damage, and potentially improve endurance capacity.

A recommended dose of 3-6 grams per day of L-citrulline is recommended, with side effects being very rare within this range.

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This article has been reviewed and fact-checked by a certified nutritionist, and only uses information from credible academic sources.