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 .
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 .
This is because nitric oxide relaxes the smooth muscle cells that would otherwise be constricted .
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 .
Following oral l-citrulline ingestion, circulating l-arginine concentrations peak after ~1-2 hours .
Nitric oxide released from the blood vessels initiates a signaling cascade that ultimately increases vasodilation by relaxing smooth muscle cells .
As individuals with impaired cardiovascular systems often see poor nitric oxide production and bioavailability, this could be important to preventing cardiovascular disease .
Keep in mind, the current data does not show short-term benefits to a single dose of L-citrulline , and supplementation needs to continue for at least a week for the vasodilatory effects to occur .
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 .
The current science also supports the idea that l-citrulline may protect against endothelial dysfunction that are initially cause by poor dietary habits.
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 .
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 .
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 .
Specifically, endurance athletes taking citrulline were able to cycle for ~10% longer before they reached the point of exhaustion .
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 .
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 .
This is backed by a few different studies where 15 grams of L-citrulline has not shown any negative side effects .
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 .
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.