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Pumped up!? Can citrulline really improve athletic performance?

Citrulline is a non-essential amino acid that could boost performance in theory. But does it do so in fact? Here, we review a recent meta-analysis examining this question.

Study under review: Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis.

Introduction

Nutritional supplementation is a common strategy used by both athletes and recreationally active people looking to improve their physical performance. In recent years, sports supplements that are believed to enhance performance by increasing nitric oxide (NO) production, often labeled “NO boosters”[1], have been getting a lot of attention. One such supplement is citrulline.

Citrulline[2] (or L-citrulline) is a non-essential amino acid, meaning that it is naturally produced in the body. Its name is derived from Citrullus vulgaris, the Latin name for watermelon[3], from which it was first identified and isolated in 1930, as it is a rich dietary source of citrulline. Unlike some amino acids, it is a non-proteinogenic amino acid[4], which means that it is not used to build proteins. That doesn’t mean that these amino acids are without physiological function, though. Citrulline ingestion may positively affect physical performance through its effects on NO production.

Specifically, citrulline ingestion has been shown to increase[5] blood arginine levels in humans. Since arginine is the main substrate[6] for the synthesis of NO, it is believed that citrulline ingestion may indirectly increase NO production, as depicted in Figure 1. In turn, given the role of NO in vasodilation[7], mitochondrial respiration[8], calcium handling[9], and glucose uptake[10], greater amounts of NO may improve muscle function and reduce fatigue.

Independently of its potential effects on NO production, citrulline may also positively impact performance through its role in the urea cycle, also shown in Figure 1. During intense exercise, there is an increase in the production of ammonia in the exercised muscle, which is thought to contribute[11] to the development of exercise-induced muscle fatigue. In order to prevent this accumulation of ammonia, the urea cycle[12] in the liver eliminates ammonia in the form of urea. As citrulline is converted to arginine in the kidneys, and arginine is degraded into ornithine in the liver, releasing urea, citrulline can potentially indirectly[2] improve ammonia clearance through the urea cycle.

Although citrulline supplementation may, theoretically, improve high intensity strength and power performance, the results from randomized controlled trials have been mixed, with some studies[13][14] finding beneficial effects with citrulline supplementation, and other studies[15][16] reporting no differences between the supplementation and placebo groups. The study under review is a meta-analysis that pooled the available trials together to examine the overall impact of acute citrulline supplementation on strength and power outcomes.

Citrulline is a non-essential amino acid that is being investigated for its potential beneficial effects for physical performance. While the exact mechanisms through which citrulline may improve performance are not yet completely understood, they may be related to the increased nitric oxide production that follows citrulline ingestion, as well as to a potential increase in ammonia clearance through its facilitative effect on the urea cycle. However, the results from the available trials examining the ergogenic effects of citrulline supplementation have been mixed. The study under review is a meta-analysis that aimed to assess the efficacy of citrulline supplementation for improving high-intensity exercise performance outcomes.

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