Is Citrulline Malate the Best Pre-workout Ingredient for Increased Endurance?

Citrulline Malate has gained a solid reputation as a powerful fatigue fighter, leading many to consider it a crucial pre-workout compound. Formulated in the body during the urea cycle expressly to dispose of nitrogenous waste (nitrogen-containing metabolic waste), the heralded workout intensifier does much more than increase physical endurance, especially when combined with malic acid, which gives it greater stability and bioavailability.
In addition to greatly extending muscular performance, Citrulline Malate increases intracellular Nitric Oxide (NO) production to enhance vasodilation and blood flow to the working muscles (thus producing the much coveted muscle pump);
  • Increases growth hormone;
  • Optimizes BCAA utilization during workouts;
  • Elevates muscle protein and creatine synthesis;
  • Improves recovery.14

In light of its many performance benefits, Citrulline Malate has become a key pre-workout intensifier for all athletes, particularly those for whom repeated bouts of heavy lifting take precedence. In fact, Citrulline Malate 2:1 has proven to be so effective that it has become an essential, alongside ingredients like Agmatine and Beta-Alanine for top Pre-Workout formulas. Keep reading to discover how this heavily-researched compound may enable you to enjoy the greatest workouts of your life.


Why Choose Citrulline Malate 2:1?

The fact is that most of the research on performance enhancement has been done on Citrulline Malate not just Citrulline on its own. Together with Malate, Citrulline has enhanced stability as a molecule and Malate has been shown in research to have the ability to play a role in Nitric Oxide production. Malate plays a key role in the TCA (or Tricyclic Acid) cycle (also known as the Krebs Cycle) that produces energy in the body. While it is true that Citrulline is the true “driver” of the two and that Malate is more prevalent in the body, so Citrulline Malate 2:1 provides the best of both worlds, stability and effectiveness. 

Extending Intensity
Of all its performance-enhancing benefits, Citrulline Malate is perhaps best known for its fatigue fighting properties.4, 7, 8, 10, 16 As mentioned, Citrulline is produced during the urea cycle in which nitrogenous waste is excreted from the body. During this process, Citrulline, when produced naturally, sucks up and expedites the removal of excess metabolic waste. Citrulline supplementation supercharges the urea cycle. Ammonia (comprised of three nitrogen molecules) is thus removed from the working muscles at a much faster rate, before it can produce the much-dreaded muscle fatigue.
By accelerating ammonia clearance from the blood, Citrulline helps postpone the inevitable decrease in muscle pH that accompanies continued training intensity. When blood pH drops, muscle tissue becomes more acidic, fatigue rapidly ensues and the muscles stop short of applying maximum effort. 14 In addition, Citrulline Malate has been shown to increase oxidative ATP (Adenosine Triphosphate) production by up to 34% and is therefore particularly effective when engaging with the iron. 12 The primary fuel source for anaerobic glycolysis, ATP ultimately dictates the amount of work a lifter can perform. When increased via Citrulline supplementation, ATP is more efficiently synthesized to provide a decided edge in muscle endurance. One study highlighted Citrulline Malate’s effectiveness by demonstrating a 53% repetition increase and a 100% response on the last set among Citrulline Malate subjects.3, 12, 14 In this study, Citrulline Malate was shown to negate the training-induced fatigue that would normally signal the end of a grueling set. In a trial held across six gyms in which several parameters of muscular performance were assessed, a group of male strength athletes received 8g of Citrulline Malate prior to being tested on the bench press. Another group received a placebo.

Each group was assessed on repetitions completed on the flat bench press at 80% of 1RM (One Repetition Maximum) before to stopping due to exhaustion. The Citrulline Malate subjects performed 19% more repetitions than the placebo group and a staggering 53% more on the last set. 12 Muscle fatigue was significantly reduced in the Citrulline group, showing what smart lifters have known all along: that Citrulline Malate keeps you training harder, for longer. It was concluded that more anaerobically-produced ATP was made available via Citrulline Malate intake, which in turn enabled a significant improvement in the oxidative processes vital to extending workout performance.3 In a similar study, conducted in two-parts 18, 19 similar outcomes were experienced among a population of advanced level resistance-trained men. Each performed upper and lower body resistance exercises at 60% of 1RM. Results showed Citrulline Malate ingestion to have significantly increased repetitions performed for each exercise.18    


    Research also shows that Citrulline Malate ingestion can promote faster post-training phosphocreatine replenishment.3 A phosphorylated creatine molecule used by the body as a rapidly mobilizable reserve of high-energy phosphates, phosphocreatine is rapidly depleted during resistance training. Its replenishment and adequate supply is thus vital when seeking to optimize training performance. Citrulline Malate supplementation has also been shown to


enhance insulin sensitivity to improve nutrient partitioning thereby ensuring greater training energy resources and less fat storage.9, 14 Citrulline Malate may also increase growth hormone (GH) levels beyond those experienced when training without CM.14 Citrulline increases blood levels of the amino acid arginine to enhance Nitric Oxide (NO) production. Among its many functions, arginine inhibits the release of growth hormone inhibiting hormone (GHIH), or somatostatin, which normally inhibits GH production. By doing so, arginine increases GH output from the anterior pituitary gland which in turn leads to higher blood levels of GH.


The muscle-building benefits of GH are widely known as is the fact that GH is released in large quantities during sleep. Less well known is the fact that GH may also be released in abundance during workouts, thus promoting even greater gains in muscle size and strength.6 GH can also, due to increased lipolysis, increase fat burning when working out. This means that more GH may encourage more fat to be released from fat cells to be utilized as another energy source. Citrulline Malate greatly enhances the fat-burning/muscle-building benefits of intra-workout GH production.19 

Faster Recovery
While some people use muscle soreness to gauge workout progress, and indeed DOMS can signal training effectiveness, it’s important to note that post-workout pain is by no means a mandatory muscle growth determiner and may even be a limiting factor. In fact, sore muscles may impair strength for days and may even compromise athletic performance (in part by decreasing muscle recruitment patterns and range of motion at the joint). Muscle soreness may also increase the likelihood of injury while decreasing one’s motivation to hit the weights hard.13 Among Citrulline Malate’s many performance benefits is its ability to attenuate post-workout muscle soreness.12 Citrulline may also aid in recovery by optimizing the post-workout healing process. In one study, researchers gave Citrulline Malate to a group of professional male cyclists (compromised immunity and illnesses such as upper respiratory infections are common among this demographic in light of the intensive training methods used to achieve faster race times).15

It was found that those who took the Citrulline Malate experienced reduced and delayed onset of the immunosuppressive mechanisms that are usually noted following intense training. The researchers concluded that Citrulline Malate may help the body to heal faster from intense training while enabling hard training athletes to avoid symptoms that are generally associated with overtraining. 

Pumping Up
As noted, Citrulline increases plasma levels of the Nitric Oxide (NO) boosting amino acid arginine within the body.5 And what’s more, it appears to perform this role even better than supplemental arginine.17 By increasing arginine endogenously, Citrulline Malate greatly enhances blood flow, oxygen delivery and the uptake of glucose and other nutrients into the working muscles.1, 5, 17 Massive muscle pumps and a steady supply of energy are but two favorable outcomes.  
Increased blood flow greatly enhances energy and endurance as oxygen and nutrient delivery to the working muscles is increased beyond normal levels. Because blood is more than 50% water, when we train, our muscle cells create waste products that attract a greater than normal amount of H2O. With increased Citrulline-induced blood flow, more water is pumped into the muscles. This produces the profound pumping sensation sought by lifters at all levels.
As with all effective supplemental strategies, it’s always best to take a range of products which exert synergetic effects. And it appears that Citrulline Malate, when taken with another of IMPACT Igniter’s key performance ingredients, N-Acetyl-L-Cysteine (NAC) (a precursor to the potent antioxidant glutathione), will further increase the muscle volumizing NO beyond levels experienced when taking only the Citrulline.
A randomized, double-blind, placebo-controlled, human clinical trial in 66 healthy males recently demonstrated that 200mg of glutathione and 2g of Citrulline (taken over one week of daily oral supplementation) greatly enhanced NO levels.11 In this study the Citrulline Malate and glutathione increased nitrate and nitrite levels (substrates for NO synthesis) more than Citrulline Malate alone. The researchers concluded that the mechanism responsible for the synergetic effect between Citrulline Malate and glutathione is glutathione’s ability further enhance the release of NO from arginine. It was also concluded that not only were blood NO levels increased via the Citrulline/glutathione combination but the NO increases were sustained for longer periods compared to a placebo and that Citrulline and glutathione may also play a role in muscle protein synthesis and muscle performance when combined with resistance training. 
More Than a Fatigue Fighter
Citrulline, as an important part of the urea cycle, is a crucial factor in reducing toxic metabolites and extending muscular endurance. When taken in supplement form its endurance-boosting benefits are greatly enhanced and further benefits can also be achieved. When combined with Malic Acid (Malate), a substance that has potent fatigue fighting properties of its own, Citrulline’s benefits are further extended. Ideally to be taken as part of a comprehensive pre-workout formulation, this muscle-building mandatory is synergistically compatible with a range of performance compounds, most notably glutathione which is produced in response to the ingestion of NAC. Increased muscle pumping, greater blood volume, enhanced amino acid/creatine assimilation and growth hormone production, and faster recovery are all possible with quality Citrulline Malate supplementation. Use it as part of your pre-workout strategy to extend performance and further ignite muscle growth.   Looking for a pure Citrulline Malate 2:1 supplement? Looking for Citrulline Malate 2:1 in a Pre-Workout?
1. Barbul, A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN J Parenter Enteral Nutr. 1986 Mar-Apr;10(2):227-38. 2. Briand, J., et al. Use of a microbial model for the determination of drug effects on cell metabolism and energetics: study of citrulline-malate. Biopharm Drug Dispos. 1992 Jan;13(1):1-22. 3. Bendahan, D., et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. British Journal of Sports Medicine 2002;36:282-289. 4. Cunniffe, B., et al. Acute CM supplementation and high-intensity cycling performance. Journal of strength and conditioning research/National Strength & Conditioning Association (2016). 5. Dhanakoti S. N., et al. Renal arginine synthesis: studies in vitro and in vivo. Am J Physiol. 1990;259:E437–E442. 6. Godfrey, R. J. et al. The exercise-induced growth hormone response in athletes. Sports Med. 2003;33(8):599-613. 7. Goubel, F., et al. Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins. Can J Physiol Pharmacol. 1997 Mar;75(3):205-7. 8. Hickner, R. C., et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006 Apr;38(4):660-6. 9. Hisae, Y., et al. L-Citrulline increases hepatic sensitivity to insulin by reducing the phosphorylation of serine 1101 in insulin receptor substrate-1. BMC Complement Altern Med. 2015; 15: 188. 10. Janeira, M. A., et al. (1998). Citrulline malate effects on the aerobic-anaerobic threshold and in post-exercise blood lactate recovery. Medicine and Science in Sports and Exercise, 30(5), Supplement abstract 880. 11. McKinley-Barnard, S., et al. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. Journal of the International Society of Sports Nutrition 12.1 (2015): 1. 12. Perez-Guisado, J., et al. Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness. The Journal of Strength & Conditioning Research 2010;24 13. Poliquin Group. Nine amazing Ways to reduce Post-Workout muscle Soreness. [Online] – retrieved on 26.10.17 14. Sureda, A., et al. l-Citrulline-malate influence over branched chain amino acid utilization during exercise. European Journal of Applied Physiology, 2010;110(2):341-51. 15. Sureda, A., et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35 16. Takeda, K., et al. Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo). 2011;57(3):246-50. 17. Wijnands K. A., et al. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5) 18. Wax, B., et al. Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males. J Diet Suppl. 2016;13(3):269-82. 19. Wax, B., et al. Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. J Strength Cond Res. 2015 Mar;29(3):786-92.

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