What does citrulline malate do? More importantly, does citrulline malate work? How does it increase Arginine levels?

Further Reading:
https://muscleandstrengthpyramids.com...
https://examine.com/supplements/citru...

To understand how citrulline malate works we need to talk about a couple processes that happen within the body.

The urea cycle, and the nitric oxide cycle.

First the Urea cycle.

When you perform an intense activity, Ammonia levels in the blood increase, especially so when you perform intense activity that requires high amount of strength. https://www.ncbi.nlm.nih.gov/pubmed/6...)

Luckily our body has a system to eliminate this ammonia which is so detrimental to our bodies and performance. The cycle is called the Urea Cycle, and as the name suggests, it exists in our body to transform this toxic and problematic ammonia, to a comparatively less toxic substance, Urea, after the cycle Urea then gets sent to the kidneys through the blood, and is from there excreted through your urine.

It relies on three amino acids, citrulline, ornithine, and arginine, here’s how it works

In the mitochondria of a liver cell, Ammonium is turned into carbomyl phosphate.

Ornithine combines with that to form Citrulline (hey wasn’t that what we were supplementing though? Dont worry ill get to that). Anyways the citrulline then leaves the mitochondria combines with aspartate and forms arginino succinate, which then transforms again into arginine, and finally an enzyme acts on that, turning it into two things ornithine to feed back into the cycle, and do it again, and Urea, which leaves your body in the form of pee.

Now that this Ornithine is back it can go back into the mitochondria, grab another ammonia (which technically is packaged up for it as carbamoyl phosphate) and do it all again. The limiting factor here though is the available Ornithine, the more ornithine, the faster the body can clear away that fatigue inducing ammonia.

Before we can see how citrulline ties all of this together and turbo charges this system, we need to look at one other system.

The nitric oxide cycle.

In the nitric oxide cycle, that same amino acid, arginine converts into citrulline, and in the process gives off nitric oxide and via some enzymes it turns into argininosuccinate, and then back into arginine. Nitric oxide is important for signalling to increase blood flow, which helps with the pump effect.

I know what you’re saying at this point well Arginine is both a precursor to a system that clears away ammonia , and its required to release NO which helps with blood flow and pumps, so why are we talking about citrulline malate.

Unlike taking an arginine supplement, citrulline is very bioavailable when taken and because it gets immediately converted into arginine in the kidneys, amazingly, Citrulline is better able to increase arginine levels, then arginine itself! This increase also comes in the form of a more controlled release.

Because supplemental citrulline is turned into arginine in the kidneys it can double arginine levels, and since arginine converts to ornithine it also is found to double ornithine levels.

So what are the implications of this.

Studies have found that taking an L-Citrulline supplement can improve physical work output, endurance, and reduce fatigue.

In one of these studies participants lifted 80% of their bench and leg press press 1RM./ They performed multiple sets with each one going to failure. (https://www.ncbi.nlm.nih.gov/pubmed/2...

One group took 8g of citrulline malate while another group consumed a placebo. The group that consumed the citrulline malate performed significantly more reps and self reported a lower RPE.

One criticism with this study though, is that they were only given one minute of rest between sets, which anyone who powerlifts knows is much shorter than a standard rest between sets.

In two other studies though, similar increases were found, in both of these studies participants took a three minute rest between sets. In all of these studies, increases came over time, and were much more noticeable in the later sets.

For example in the one of the studies on CM it was noted that while 73% of the subjects reported nonresponse on set 1, all subjects reported response on set 8. https://www.ncbi.nlm.nih.gov/pubmed/2...
Increases in nitric oxide are more difficult to measure, however studies have noted an increase in the biomarkers which would suggest an increase in nitric oxide levels.
Also notably Citrulline Malate seems to have a profound effect on reducing Delayed Onset Muscle Soreness, also called DOMS, of which there was a reduction seen of 40%... sort of like the real reduction we’ve seen of Dom on youtube :(
Which is a perfect segway into the final benefit, In men with erectile dysfunction who given just 1.5 g of citrulline per day, after one month, half reported a major improvement in the quality of their erections.