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All About Citrulline

Several decades ago Arnold started to talk about the importance of the “pump”. In recent years, the increased research into weight lifting has proven that the pump, or its scientific name “Cell Swelling” is actually a key mechanism behind hypertrophy (muscle growth).

Several supplements are emerging which attempt to tap into this mechanism. Although most lack supportive research, Citrulline is one of a few that could provide some impressive results.


L-Citrulline is an amino acid and is turned into L-Arginine once it reaches the kidneys. Despite what you may be thinking, L-Citrulline is actually more beneficial than L-Arginine.

One issue with L-Arginine supplementation is the poor absorption rate when it passes through the intestines. L-Arginine is also used for multiple processes within the body, meaning some of the arginine you supplement with will be diverted away from the muscles.

L-Citrulline’s main mechanism is its action of increasing Nitric Oxide (NO), primarily caused by the increase of L-Arginine. Nitric Oxide plays an important role in vasodilation and blood flow. When you increase NO levels, the blood vessels dilate or relax, which in turn enables more nutrient rich blood to reach the working muscles. Remember, blood also carries oxygen to the muscles and also plays a role in removing deoxygenated blood from them.

This balance between fresh oxygenated blood and deoxygenated blood is important, helping our muscles contract with full intensity and resist fatigue. The deoxygenated blood also plays a role in waste product removal. Waste products, such as hydrogen ions increase with each rep. Eventually, these affect muscle PH levels and cause acidosis, leading to fatigue and weakness. In a gym based setting, this is the intense burn you feel towards the end of a set, which most people wrongly associate with lactic acid.

As mentioned at the start, L-Citrulline may also improve cell swelling, one of the 3 main mechanisms behind muscle growth. In addition to that “awesome feeling”, cell swelling initiates a cascade of important physiological processes. These include an increase in Muscle Protein Synthesis, a primary pathway behind muscle growth.

Citrulline may also help reduce fatigue via the reduction of “ammonia”, which is discussed in the next section.

Citrulline for Reducing Ammonia – A Key Driver in Fatigue

During high-intensity exercise, the concentration of Ammonia increases. Ammonia activates phosphofructokinase (PFK). This prevents or blunts a key role in ATP production (energy).

Ammonia also prevents the oxidation of pyruvate to acetyl CoA, which is a key step in the production of energy during exercise. Therefore, when ammonia blocks this process, we run out of energy and breath, leading to exhaustion.

The increase in PFK also causes a decline in the muscle’s pH level, i.e. it becomes more “acidic”. As discussed in the section above, this increases by-products, such as Hydrogen ions, leading to fatigue.

Due to Citrulline’s role in the urea cycle (as discussed at the start), it may help to remove or “detox” the ammonia via the liver.

In summary, Citrulline will help reduce ammonia building, which will help delay the onset of fatigue when training. This could obviously allow for more reps, which may increase muscle damage, total session volume and cell swelling, all key mechanisms of muscle growth.

Research Proven Benefits of Citrulline

Citrulline is well known for improving sports performance and may also aid in markers of health - it has even been used to treat erectile dysfunction! As you can see from the mechanisms of Citrulline, it can play an important role in any cell swelling and may be key for your pre workout mix.

Here are some of the research proven benefits that L-Citrulline may provide (references below):

  • Reduces fatigue
  • Increased work capacity
  • Reduced muscle soreness
  • Increases ‘Nitric Oxide’ levels
  • Improves blood flow
  • Increases arginine levels
  • Increases Growth Hormone levels post workout
  • Increases Amino Acid uptake
  • May aid in ATP (energy) resynthesis between sets
  • May allow for increased training volume, a key mechanism behind muscle growth.
  • Decrease blood pressure
  • May improve immune system function by priming the neutrophils cells
  • You get an awesome, skin splitting pump!

L-Citrulline Research

Study 1: Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness (Perez-Guisado et al. 2010).

Forty one men performed 2 chest training sessions (16 sets per session) and consumed Citrulline or taste-matched placebo before the session. The number of reps performed was drastically higher in the Citrulline group compared to placebo; this increased as the session progressed.

At 24 hours post, muscle soreness was almost double in the placebo group compared to non-placebo. At 48 hours post it was still 30% higher in the placebo group. As you can see from the graph, some individuals doubled the reps they could performed in set 4 (white = Citrulline, Black = placebo).

This is one of the few studies that stimulate a bodybuilding type workout, using flat bench press, incline bench press and dumbbell flys, which makes the results much more applicable to our population.

Study 2: Effects of Citrulline Supplementation on Fatigue and Exercise Performance in Mice (Takeda et al. 2010).

This study compared the effects of Citrulline supplementation in mice during an aerobic exercise test to fail. Before you disregard this finding because it was studied in mice, most research initiates in mice as they have a very similar physiology to humans and allow for more controlled, detailed testing.

Mice consumed the Citrulline 30 minutes prior to the exercise test. The non-supplement group (given water) managed 15 minutes until exhaustion, whereas the Citrulline group managed nearly 25 minutes.  Blood lactate levels were also markedly lower for the Citrulline group. Lactate levels are often used as a marker of fatigue, as they rise in correlation with by products that cause fatigue, such as hydrogen ions. This may be one mechanism for the improvement in the Citrulline group, along with the detoxification of ammonia which is discussed above.

Citrulline is a new exciting supplement with years of research in store. It’s still early days for Citrulline. However, the mechanisms of actions along with the few weight training studies available do already show benefit. New data is also continually emerging showing Citrulline may have added blood flow and health benefits.

While Citrulline may not be as well researched as a supplement such as whey protein or creatine, due to factors like its low cost, no reported side effects (when dosed correctly) and mechanisms of action, it is quickly becoming the next big pre workout supplement within the bodybuilding world.

In theory, Citrulline may well have the biggest effect in higher rep, metabolic workouts or when using techniques such as those in Kris Gethin’s DTP, or if using drop sets and supersets etc.

Try using 4-6g (larger 200lb + individuals may need the upper range) of KM Citrulline or PRE-KAGED (containing 6g of Citrulline) in your pre workout mix.


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