A critical review of citrulline malate supplementation and exercise performance

Abstract

As a nitric oxide (NO) enhancer, citrulline malate (CM) has recently been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance, as well as the recovery of muscular performance. The mechanism has been associated with enhanced blood flow to active musculature, however, it might be more far-reaching as either ammonia homeostasis could be improved, or ATP production could be increased via greater availability of malate. Moreover, CM might improve muscle recovery via increased nutrient delivery and/or removal of waste products. To date, a single acute 8 g dose of CM on either resistance exercise performance or cycling has been the most common approach, which has produced equivocal results. This makes the effectiveness of CM to improve exercise performance difficult to determine. Reasons for the disparity in conclusions seem to be due to methodological discrepancies such as the testing protocols and the associated test-retest reliability, dosing strategy (i.e., amount and timing), and the recent discovery of quality control issues with some manufacturers stated (i.e., citrulline:malate ratios). Further exploration of the optimal dose is therefore required including quantification of the bioavailability of NO, citrulline, and malate following ingestion of a range of CM doses. Similarly, further well-controlled studies using highly repeatable exercise protocols with a large aerobic component are required to assess the mechanisms associated with this supplement appropriately. Until such studies are completed, the efficacy of CM supplementation to improve exercise performance remains ambiguous.

Keywords: High-intensity exercise; Metabolism; Nitric oxide; Resistance training; Supplements.

Fig. 1

A schematic representation of the mechanisms associated with citrulline malate supplementation. Bold denotes the active ingredient. Left: NO-derived mechanism, Right: Ammonia clearance mechanism. *Denotes evidence is either speculative or has only been observed in mice. (Schematic created in BioRender.com)

Fig. 2

A schematic representation of the mechanisms associated with citrulline malate supplementation. Bold denotes the active ingredient. Left: Increased bioavailability of malate mechanism, Right: Increased efficiency of Malate Aspartate Shuttle (MAS). *Denotes evidence is either speculative or has only been observed in mice. (Schematic created in BioRender.com)