We’re always on the lookout for the next ergogenic supplement, but only every so often does one catch our eye. Citrulline (i.e. citrulline malate or CM) is a supplement that gained popularity with the rise of so called “nitric oxide stimulators” and seems to have an effect as an acid buffer, at least in certain medical conditions. Could citrulline actually be ergogenic or even stimulate muscle blood flow through nitric oxide? Given the potential for performance and body composition benefits, let’s take a closer look at this supplement and determine whether it’s something you should be using.
As is common in supplement marketing, the claims about CM grossly exceed the supporting data. There are only a couple of related published exercise studies and they’re terrible (at least from our perspective). Granted, there are a few unpublished studies showing performance benefits from CM, but if unpublished supplement research were valid, we’d all be using HMB.
Now, I’m not saying that unpublished work is inherently wrong (I can see the straw men being built now), but it has (sadly) become a quick and dirty marketing tool. As a result, caution should be exercised in evaluating its efficacy/applicability. Using this as the perfect segue…if you want more information on that research, you can find it in plenty of other articles—right next to the CM advertisement.
Enough about the garbage! Let’s move on to the…trash.
Ergogenic evidence
One published study showed that CM supplementation improved aerobic function during a hand grip exercise (2). Pretty impressive, right? Well, there are a couple of small (think Jurassic Park sized) holes in the study. There was no placebo group. Seriously, a supplement study with 18 subjects didn’t use a control. Although they tried to get around this, it begs the critical question of, why would you ever want to?
Exercise performance wasn’t actually measured. (Again, I’m serious.) Instead, biochemical measures were taken, which is about as useful to us as not using a placebo group. Even though you’ll see this study referenced elsewhere and it remains somewhat interesting (in an optimistic sense), it doesn’t mean anything for us.
Citrulline ergolytic?
The other CM study of interest showed that CM supplementation actually had a deleterious effect on treadmill running performance (4). It decreased time to fatigue and increased the perceived exertion of the subjects (i.e. it made the training feel more difficult). Unfortunately, the researchers divided the subjects up into trained and untrained groups and gave them different exercise protocols.
Why was this not better controlled? Once again, this division of groups, which seems like an afterthought, confounds the result. This leaves us with another very interesting finding that we can’t definitively apply.
The nitric oxide stimulator
Even if we don’t have a clear picture about CM supplementation and exercise in healthy people, it still has the claim of stimulating nitric oxide (NO) levels. NO is proposed to stimulate muscle blood flow and subsequently increase performance and stimulate muscle growth. The latter part actually has merit because increasing blood flow to muscle can dramatically improve nutrient delivery.
In fact, this is why pre-workout meals are still the most anabolic nutritional supplementation practice we know. This is why I discussed the application of this in the Anabolic Index. The big question is whether CM supplementation can actually accomplish this.
Citrulline and arginine
The basic idea behind “blood flow stimulators” (a largely fictitious name) is that arginine can be converted to nitric oxide, which stimulates blood flow. So if you provide more arginine, you’ll have more nitric oxide and even more blood flow. For a full review of this oversimplified inanity, see the article “Consumer Alert: The NO/Arginine (a.k.a. “Nitric Oxide Stimulator”) Scam” (1).
But how does citrulline play into this? Well, citrulline is co-produced with nitric oxide (figure 1) so it has to be involved somehow.
What’s interesting is that citrulline can be converted back into arginine. In fact, ingested citrulline actually improves blood arginine levels more than arginine ingestion itself (5)! Although this is fascinating in a science geek sort of way, it still doesn’t say much about NO production or blood flow. That’s because blood arginine levels don’t have much to do with NO production in healthy people. Increasing or even decreasing serum arginine has no direct effect on nitric oxide.
Although the study in question (5) showed no change in blood flow with CM supplementation, there was a change in a specific arginine ratio, and this was correlated to blood flow. In other words, there may be hope for CM and blood flow yet. This is likely mediated through insulin, which is postulated to be the predominant mechanism through which arginine affects blood flow (1, 3), but I’ll save that discussion for another time.
A minor issue with the study is that they specifically chose subjects who had naturally low to normal blood flow, which makes them far more likely to respond to citrulline/arginine supplementation. After all, only 3 grams of citrulline was used, which would yield only a small increase in blood arginine. Examine this in the context of a high protein diet and you’re even less likely to experience a benefit. However, a complete discussion is beyond the scope of this colloquial review.
Conclusion
Citrulline malate is a curious supplement that has been shown to both improve and worsen performance, each from a questionable study. What’s absolutely fascinating, however, is the fact that citrulline ingestion can elevate blood arginine even more than consuming arginine. High doses given in a fasted state may affect nitric oxide levels, likely through an insulin-related mechanism. Although it currently posses an anabolic index score of 0, there is potential for this to improve for people with naturally suboptimal blood flow.
Final recommendation: Given even the small possibility of an ergolytic effect and likelihood of an absence of effect altogether, citrulline is something I wouldn’t pay to consume. Stay tuned for more information. As always, raise your expectations.
Raise the Barr.
References
- Barr D (2005) Consumer Alert: The NO/Arginine (a.k.a. “Nitric Oxide Stimulator”) Scam. At: http://www.raisethebarr.net/index.php?/Nitric-Oxide-Stimulators-I.html.
- Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJ (2002) Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med 36(4):282–9.
- Calver A, Collier J, Vallance P (1991) Dilator actions of arginine in human peripheral vasculature. Clin Sci (Lond) 81(5):695–700.
- Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M (2006) L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 38(4):660–6.
- Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Böger RH (2008) Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 65(1):51–9.