L-Citrulline: The Anti-Fatigue Effect

L-Citrulline: The Anti-Fatigue Effect

L-Citrulline: The Anti-Fatigue Effect

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By Crom Arus

If you’re a regular in the gym and also interested in the wide array of supplements, I bet you know already about the amino acids l-citrulline and its effects on arginine and NO synthesis. Therefore, it probably won’t come to you as a surprise that a lot of manufacturers add this ingredient to their pre-workout formulas, to enhance pump, blood flow and nutrient delivery to muscle tissue (usually mixed with other “pump substances” like arginine-alpha-ketoglutarate (AAKG) or ornithine-alpha-ketoglutarate (OKG)).

(Source: Wikimedia.org / Yikrazuul ; CC Licence)

Chemical structure of Nitric Oxide (NO) (Source: Wikimedia.org / Yikrazuul ; CC Licence)

While it makes sense to use arginine to facilitate increased blood flow (after all, it serves as a direct interface between the urea cycle and NO synthesis [1]), citrulline and ornithine serve as precursors to the aforementioned amino acid. So what is the reason for citrulline’s rising popularity when it comes down to increase NO synthesis? Wouldn’t it make more sense to supplement arginine instead of the other two substances?

Well, in theory it does but there are two practical reasons to use citrulline:

  • 1st reason: Citrulline raises the plasma concentration of arginine to a greater degree and for a longer period of time than arginine consumption itself [2][3].
  • 2nd reason: Citrulline can improve your endurance and thus delay onset of fatigue while working out [2][3].

Today, we’re going to take a closer look at the second effect.

L-Citrulline: The Anti-Fatigue Effect

L-Citrulline-Malate: What is it?

Citrulline - Anti Fatigue

Burning sensation and fatigue: Accumulation of metabolic waste products inhibits further mechanical work. (Source: Flickr / istolethetv ; CC Licence)

As already said, citrulline is a metabolite of the amino acid ornithine (Carbamoyl phosphate + Ornithine = Citrulline) in the urea cycle.

Before we delve deeper into the topic of citrulline’s anti-fatigue effects, we should clear up why (muscle) fatigue occurs in the first place: Every time you work out vigorously and exercise until exhaustion the body starts building up metabolites, which start to prevent further mechanical work and movement.

Exhaustion in itself is not optional. The longer and harder you work out, the more metabolites accumulate in muscle tissue, leading to an acidic environment (pH ↓), until no more work can be done. You probably know the burning sensation, which pays a visit to you every time you go all out, right? There are several of these metabolites, like H+ ions, lactic acid and… Ammonia.

Every time you engage in high intensity exercise, the ammonia concentration in muscle tissue begins to raise. Now, Ammonia (NH3) is a compound, consisting of one part nitrogen and three parts hydrogen and it is quite toxic to the human body in high concentrations – it’s a metabolic waste product that needs to be get rid off.

So, what can we do to prevent a toxic build-up of ammonia in muscle tissue? Our body can either combine it with glutamate to synthesize glutamine (which then gets transported to the liver, where it contributes to a process called glucogenesis) or it can be converted to carbamoyl phosphate (with the help of carbon dioxide), before entering the urea cycle, where it gets converted to citrulline.

There are some interesting studies which show, that the supplementation with citrulline is an efficient way to raise plasma concentrations of arginine – which is known to increase NO synthesis, which leads to an improved blood flow and therefore to a better nutrient supply of muscle tissue and disposal of metabolic waste products (like ammonia).

It should come as no surprise that a better supply of nutrients and a faster disposal rate of work-inhibiting waste products should lead to a better performance and improved endurance.

But why is citrulline coupled with malate…?

Malic acid for sour taste in fruits

But why are you so sour? Malic acid adds a sour flavor to fruits. (Source: Wikimedia; Abhijit Tembhekar ; CC Licence)

Once you take a close look at your favourite pre-workout booster or pump supplement, you should notice that citrulline usually comes in combination with malate, a salt form of malic acid which contributes to the sour taste of fruits (e.g. apples).

Malates serve as intermediates in the (energy-producing) citric-acid cycle. Citrulline is bound to malate to ensure better stability, so that the substance can be transported where it is needed. This combination is quite effective, since malic acid is known to help in the recycling process of lactic acid – another metabolic waste product, which accumulates in muscle tissue with ongoing high intensity exercise.

L-Citrulline Malate for more endurance and less DOMS

Once you start your workout program, the environment in muscle tissue begins to change – there is a drop in the pH value. If this drop is severe enough, it will prevent important energy producing processes in the muscle cells – and your muscles get fatigued.

Citrulline Malate & Resistance training

Citrulline raises endurance

Improve your bench press by 52,92 %? Spanish study proves effectiveness of citrulline in experienced weightlifters. (Source: Flickr / navcent ; CC Licence)

Let’s see how well citrulline malate performs in practice. Is it really that useful?

Thanks to Perez-Guisado/Jakeman (2010) we can try to formulate a good answer to this important question. These scientists were interested in the anti-fatigue effects of citrulline malate and recruited experienced male weightlifters to see how performance changes during bench press exercise. These 41 athletes received either citrulline malate or a placebo.

The outcome? Those athletes, who received the real supplement improved their number of repetitions by astonishing +52.92 % when compared to the placebo group [4]. But not only that – athletes who received citrulline malate also reported less muscle stiffness (↓40 %, when compared to the placebo group 24 & 48 hours post-workout).

However, there was a slight side-effect, since 14.63 % of those athletes, who received the supplement, reported about digestive problems due to citrulline consumption.

Citrulline Malate & Endurance training

Another group of scientists studied the effect of citrulline supplementation (or arginine) in cycling pros (a group of athletes, which is known for their high volume training). High volume training may lead to a compromised immune system, which raises the risk of illness (especially upper respiratory tract infections (“URTI”) [6])

So, to what conclusion did those Spaniards come?

Supplementation with citrulline malate (3g/day) lessened the immunosuppressive effect of high volume training to a greater degree than arginine (8g/day) [5]. This should be especially interesting for all of us, who pursue a high volume training regimen and/or are plagued with a high incidence rate of colds.

Final Words

So what will it be for you: Arginine or Citrulline?

For the last few years, arginine has been widely used as a NO booster ingredient. However, this changed after the publication of a German team of scientists, which proved the effectiveness of citrulline over arginine: 3 grams of citrulline malate should be enough to induce a raise in plasma concentration of arginine (and therefore NO synthesis). If you opt for arginine instead, you should raise the acute dosage to at least +6 grams:

„Citrulline supplementation significantly increased plasma concentration of both arginine and citrulline after the stage only in the supplemented group.” – Sureda et al. (2010)

If you’re aiming for a prolonged effect, it might be wise choice to combine several grams arginine (e.g. as AAKG) with 3 grams of citrulline (CM). However, if you experience digestive upset with large(r) doses of arginine, you should probably switch entirely to citrulline.

Personally speaking, I’ve got no experience with OKG, but I think it wouldn’t improve the outcome, if you’re already using a stack with citrulline an arginine. You can still give it a shot, though.

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Picture sources: Flickr.com; Rose Physical Therapy ; CC Licence

About the Author – Crom Arus

Dedicated weightlifter, fitness addict and anti-broscience advocate with a scientific background in supplementation.

References (Click to Expand)

[1] Wiesinger, H. (2001): Arginine metabolism and the synthesis of nitric oxide in the nervous system. In: Prog Neurobiol. URL: http://www.ncbi.nlm.nih.gov/pubmed/11275358.

[2] Sureda, A., et al. (2010): L-citrulline-malate influence over branched chain amino acid utilization during exercise. In: Eur J Appl Physiol. URL: http://www.ncbi.nlm.nih.gov/pubmed/20499249.

[3] Ochai, M.,et al. (2012): Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. In: Int J Cardiol. URL: http://www.ncbi.nlm.nih.gov/pubmed/21067832.

[4] Perez-Guisado, J. / Jakeman, PM. (2010): Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness. In: J Strength Cond Res. URL: http://www.ncbi.nlm.nih.gov/pubmed/20386132.

[5] Orozco-Gutierrez, JJ. et al. (2010): Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. In: Cardiol J. URL: http://www.ncbi.nlm.nih.gov/pubmed/21154265.

[6] Nieman, DC. (1994): Exercise, upper respiratory tract infection, and the immune system. In: Med Sci Sports Exerc. URL: http://www.ncbi.nlm.nih.gov/pubmed/8164529.


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