After the massive success of one of the first nitric oxide boosters, L-Arginine, a search was started to find the next best nitric oxide booster. For those in the know, they knew that during the process of nitric oxide synthesis, L-arginine gives up a nitrogen, which the nitric oxide synthase enzymes then bind to oxygen, in order to generate nitric oxide. This reaction then also yields L-citrulline. L-citrulline can quite readily once again acquire a nitrogen, which then turns L-citrulline back into L-arginine. This L-arginine can then go on to generate nitric oxide. Research has in fact shown that by consuming L-citrulline directly, we can actually achieve higher and more prolonged levels of L-arginine through the L-citrulline to L-arginine conversion pathway, when compared to directly consuming L-arginine!
All of the classic nitric oxide benefits can thus be found with L-citrulline supplementation. In contrast to L-arginine, the effects of L-citrulline on nitric oxide take a little bit longer to kick in, but subsequently do so for a much longer period of time. This makes L-citrulline shine for all day nitric oxide boosting. Increased nitric oxide levels are associated with more blood flow, especially to muscles. This comes in handy when we exercise, in order to increase the “muscle pump” sensation. Overall, it is a fantastic ingredient for both cardiovascular support, and general fitness, while being especially great for bodybuilders chasing the pump!
L-citrulline is an amino acid, which can be found in various food sources, most notably, watermelon. In fact, L-citrulline was first isolated from watermelons in 1914 by two Japanese researchers, Yotaro Koga and Ryo Odake. L-citrulline was named more than a decade later, by another Japanese scientist called Mitsunori Wada, who even named L-citrulline after the latin name for watermelons, Citrullus lanatus! However, we don’t consume a lot of this watermelon amino acid through our diet, and instead, it forms in our bodies from L-arginine during the process by which nitric oxide is created.
When the amino acid L-arginine encounters one of the nitric oxide synthase (NOS) enzymes, one of its nitrogens gets ripped off, and combined with oxygen by NOS, in order to generate nitric oxide. This process then also yields L-citrulline, which is simply L-arginine, minus a nitrogen. This is illustrated in Figure 1.
Figure 1. The minor difference between L-arginine and L-citrulline, which is a single nitrogen.
L-citrulline can then be converted relatively rapidly back to L-arginine, which is mostly happening during the urea cycle. As is illustrated below in figure 2. L-citrulline enters the urea cycle and is then converted to argininosuccinate via the enzyme argininosuccinate synthase. Argininosuccinate is then converted to L-arginine by the enzyme argininosuccinate lyase. At this point, the L-arginine that was generated from L-citrulline can interact with NOS again in order to generate nitric oxide.
Figure 2. The urea cycle, which can convert L-citrulline back into L-arginine
As can be spotted on Figure 2. above, L-arginine can also be rapidly turned into L-ornithine in the urea cycle, by the enzyme arginase. This is one of the concerns with orally supplemented L-arginine, because a lot of the consumed L-arginine can be converted to L-ornithine before it can interact with NOS enzymes in order to generate nitric oxide. Various studies have shown that because L-citrulline is further back in the urea cycle, orally supplemented L-citrulline actually has a much better chance of elevating L-arginine levels in areas where the L-arginine can interact with the NOS enzymes in order to produce nitric oxide. With this in mind, it is often thought that elevating L-arginine levels can be done in a more efficient manner with L-citrulline, rather than with L-arginine. One interesting thing to note here however, is that the conversion of L-citrulline to L-arginine is not instantaneous, so this does mean that the nitric oxide boosting effects of L-citrulline will be slower when compared to L-arginine. This is perhaps why some individuals actually prefer L-Arginine for its nitric oxide boosting properties, because it can potentially get to work much faster. On the other hand, while L-citrulline takes longer to elevate nitric oxide levels, it can do it over a much longer period of time, and in a much more efficient manner!
The reason why we are primarily interested in nitric oxide boosters like L-citrulline and L-arginine, is because nitric oxide is a gaseous neurotransmitter which can control the relaxation of our blood vessels. Nitric oxide does this by activating an enzyme called guanylate cyclase, which then triggers the synthesis of cyclic guanosine monophosphate (cGMP). cGMP can interact with the smooth muscles in our blood vessels, which allows them to relax. When our blood vessels are relaxed, we can pump more blood through them, and this process is called vasodilation. In the context of physical exercise, this can increase the infamous “muscle pump” sensation. The vasodilatory effect can also have a positive effect on overall cardiovascular function.
The Nitric Oxide Stack: L-Citrulline + L-Arginine Capsules
One of the benefits of L-arginine over L-citrulline, is that it can cause quicker and potentially higher peaks in nitric oxide levels than L-citrulline. However, it is not very efficient, because a lot of the supplemented L-arginine gets converted to L-ornithine by the enzyme arginase, thereby not allowing that portion of the supplemented L-arginine to rapidly turn into nitric oxide. L-citrulline bypasses the arginase enzyme, and does a better job of efficiently elevating nitric oxide levels for a prolonged period. Something very unique happens though, when L-arginine and L-citrulline are stacked together. L-citrulline actually appears to inhibit the arginase enzyme, thereby drastically increasing L-arginine bioavailability. Thus, when L-arginine and L-citrulline are stacked, you get the best of both worlds, rapid peaks in nitric oxide levels, in addition to sustained nitric oxide levels for a prolonged period of time!
The Blood Flow Stack: L-Citrulline + Reduced Glutathione Tablets
Another interesting way by which we can enhance the effects of L-citrulline, is by combining it with reduced glutathione. The nitric oxide which L-citrulline helps synthesize, has a relatively short half life, and it appears that reduced glutathione can help prolong the half life of nitric oxide. This effect helps further promote the vasodilatory effect of L-citrulline supplementation.
The Athlete’s Immune Stack: L-Citrulline + MicroZinc Capsules
L-citrulline also has a unique immune function promoting effects, which we find stacks well with the immune function promoting effects of zinc. The main reason why we decided to stack L-citrulline and zinc together is because athletes, after intense bouts of exercise, can have reduced immune function, in addition to losing a lot of zinc through their sweat. Thus, a combination of L-citrulline and zinc, can help support athletes both during and post exercise!
As a dietary supplement, take two capsules of L-Citrulline 1-2 times daily.
To gain more insight, see the L-Citrulline reviews and experiences below.
Nootropics Depot offers a 365ct. jar of high-quality L-Citrulline. Nootropics Depot’s L-Citrulline has been lab-tested and verified for both product purity and identity.
Attention: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.