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Citrulline wants to pump you up!

Nitric oxide is all the rage, but confusion abounds on what works.

Study under review: Effects of supplemental citrulline malate ingestion during repeated bouts of lowerbody exercise in advanced weightlifters


Competitive athletes are always on the lookout for a new supplement that can make them stronger or improve their performance, even if that supplement is not backed by a whole lot of scientific research. Similar to previous studies covered in Study Deep Dives on both HMB and sodium phosphate supplementation, citrulline malate is a relatively new ergogenic aid that has limited but promising research behind it.

As the name suggests, citrulline malate is made up of L-citrulline and malate. Citrulline is an amino acid made by the body. It is synthesized from glutamine, as well as from the conversion of arginine to nitric oxide. Watermelon is the only common food source that contains significant amounts of citrulline, with amounts ranging from 0.7 to 3.6 milligrams per gram of fresh weight[1]. Citrulline supplementation actually raises plasma arginine more than actually taking supplemental arginine. This is because oral arginine is broken down in the small intestine and liver, while oral citrulline bypasses liver metabolism and roughly 80% of the ingested dose can be converted to arginine in the kidneys.

The major effects of citrulline malate are depicted in Figure 1. By way of raising plasma arginine levels, some scientists hypothesize that citrulline may increase nitric oxide[2] production[3]. Nitric oxide is an important molecule involved in cell processes, including vasodilation (widening of the blood vessels, which increases blood flow, lowers blood pressure, and gets more blood to working muscles). Citrulline is also recycled to arginine[4] by endothelial cells, which is important for the muscle pump because it means that they produce their own nitric oxide substrate, which can lead to increased muscle glucose uptake and fat burning, as well as improved muscle growth. Malate is an intermediate molecule in the Krebs cycle and plays a role in energy (ATP) production and the metabolism of carbs, fats, and proteins.

Figure 1: The effects of citrulline and malate

Source: Petrovic et al. J Exp Biol. 2008 Jan.

While previous exercise studies[5][6] have found mixed results with citrulline supplementation alone, it is hypothesized that citrulline and malate may work together synergistically to provide an ergogenic effect. These benefits[7] may include reduced feelings of fatigue during exercise, increased ATP production, and increased recovery rate of the short-term energy system (phosphocreatine).

Prior to this study by Wax and colleagues, only one study[8] has tested the effects of citrulline malate on resistance training performance and found improvements in the number of reps performed during an upper-body resistance training protocol. Due to its greater muscle mass, the lower body may actually respond more dramatically to supplementation compared with the upper body. Determining whether this hypothesis is correct was one of the goals of this study. The authors investigated the effects of acute citrulline malate supplementation on lower-body resistance exercise performance, blood lactate, heart rate, and blood pressure.

Citrulline is a non-essential amino acid that may increase nitric oxide production, which could, in theory, contribute to improved athletic performance. However, tests in humans have so far had mixed results. But results in upper body resistance training when citrulline is combined with malate, a component of the Krebs cycle, were more promising. The current study tested the effects of citrulline malate on lower body resistance training.

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