madman
Super Moderator
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.
Introduction
Considerable research attention has recently been placed on the physiological signaling molecule, nitric oxide (NO) (Jones et al. 2020). Augmenting NO synthesis through exogenous substances may improve skeletal muscle function and performance through improved blood flow, contractility, and mitochondrial respiration (Stamler and Meissner 2001). Typical strategies to increase NO activity include the ingestion of green leafy vegetables and/or beetroot juice and L-citrulline (Jones 2020). Indeed, L-citrulline is known to exert positive effects on exercise performance and recovery (Gonzalez and Trexler 2020). More recently, however, a direct NO precursor called citrulline malate (CM) has been touted to have ergogenic potential, which is the combination of L-citrulline and malate (Gonzalez and Trexler 2020). The mechanisms of CM might be more far-reaching as a result, due to the synergistic impact of both components (i.e., L-citrulline and malate) at the intramuscular level (Wax et al. 2015). Specifically, malate has been suggested to increase the rate of ATP production by mitigating lactate production during states of high flux; and by doing so allowing for continued pyruvate and energy production (Wax et al. 2016). Furthermore, the malate-aspartate shuttle (MAS) may be more efficient following CM ingestion, thereby improving ATP availability (Wu et al. 2007; Agudelo et al. 2019). Based on these promising findings and additional mechanisms compared to L-citrulline supplementation alone, it is plausible to suggest CM supplementation could be a worthwhile ergogenic aid.
*Proposed ergogenic mechanisms
*Dose, timing, and safety
*Effects of citrulline malate on exercise performance
Conclusions and future directions
The lack of positive effects from CM supplementation within the existing literature is due to a number of factors, including the testing protocols not featuring a predominantly aerobic energy contribution, the lack of test-retest reliability of exercise protocols, dosing strategy (i.e., amount and timing), and the recent discovery of quality control issues with some manufacturers stated citrulline: malate ratios. Indeed, this diversity adds a level of additional noise to our ability to draw firm conclusions about the efficacy of CM supplementation on exercise performance or recovery from exhaustive exercise. Nevertheless, from the available evidence, an acute 8 g dose CM may, albeit not consistently, increase muscular endurance-strength performance (Table 1). This corroborates with a recent meta-analysis conducted at the time of writing this review, which also reported similar benefits (Vårvik et al. 2021). Whereas, there is little evidence to advocate its use in the production and maintenance of muscular power, maximal strength, recovery of muscular function, or supporting muscular adaptations currently (Table 1). Lastly, athletes wishing to explore NO enhancers are reminded that a good level of evidence exists for L-citrulline to improve exercise performance, and therefore may consider the use of this supplement whilst the intricacies of CM supplementation is discovered (Gonzalez and Trexler 2020).
Only at this point will the physiologically optimal dose of CM become clear. Due to the logistical and cost burden of conducting such a study, a simpler approach would be to assess various doses of CM (e.g., 8 vs. 10 vs. 12 g CM) on an exercise protocol that requires a predominantly aerobic energy demand and has high test-retest reliability. Furthermore, manufacturers are required to take more responsibility to guarantee that the ratio stated is what is contained within the product and researchers/practitioners should be aware of this when sourcing their product for research and/or use with athletes. Finally, those who have the resources (primarily manufacturers but also researchers) should analyze the purity of the C:M ratio to ensure they have every opportunity of achieving an ergogenic effect.
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.
Introduction
Considerable research attention has recently been placed on the physiological signaling molecule, nitric oxide (NO) (Jones et al. 2020). Augmenting NO synthesis through exogenous substances may improve skeletal muscle function and performance through improved blood flow, contractility, and mitochondrial respiration (Stamler and Meissner 2001). Typical strategies to increase NO activity include the ingestion of green leafy vegetables and/or beetroot juice and L-citrulline (Jones 2020). Indeed, L-citrulline is known to exert positive effects on exercise performance and recovery (Gonzalez and Trexler 2020). More recently, however, a direct NO precursor called citrulline malate (CM) has been touted to have ergogenic potential, which is the combination of L-citrulline and malate (Gonzalez and Trexler 2020). The mechanisms of CM might be more far-reaching as a result, due to the synergistic impact of both components (i.e., L-citrulline and malate) at the intramuscular level (Wax et al. 2015). Specifically, malate has been suggested to increase the rate of ATP production by mitigating lactate production during states of high flux; and by doing so allowing for continued pyruvate and energy production (Wax et al. 2016). Furthermore, the malate-aspartate shuttle (MAS) may be more efficient following CM ingestion, thereby improving ATP availability (Wu et al. 2007; Agudelo et al. 2019). Based on these promising findings and additional mechanisms compared to L-citrulline supplementation alone, it is plausible to suggest CM supplementation could be a worthwhile ergogenic aid.
*Proposed ergogenic mechanisms
*Dose, timing, and safety
*Effects of citrulline malate on exercise performance
Conclusions and future directions
The lack of positive effects from CM supplementation within the existing literature is due to a number of factors, including the testing protocols not featuring a predominantly aerobic energy contribution, the lack of test-retest reliability of exercise protocols, dosing strategy (i.e., amount and timing), and the recent discovery of quality control issues with some manufacturers stated citrulline: malate ratios. Indeed, this diversity adds a level of additional noise to our ability to draw firm conclusions about the efficacy of CM supplementation on exercise performance or recovery from exhaustive exercise. Nevertheless, from the available evidence, an acute 8 g dose CM may, albeit not consistently, increase muscular endurance-strength performance (Table 1). This corroborates with a recent meta-analysis conducted at the time of writing this review, which also reported similar benefits (Vårvik et al. 2021). Whereas, there is little evidence to advocate its use in the production and maintenance of muscular power, maximal strength, recovery of muscular function, or supporting muscular adaptations currently (Table 1). Lastly, athletes wishing to explore NO enhancers are reminded that a good level of evidence exists for L-citrulline to improve exercise performance, and therefore may consider the use of this supplement whilst the intricacies of CM supplementation is discovered (Gonzalez and Trexler 2020).
Only at this point will the physiologically optimal dose of CM become clear. Due to the logistical and cost burden of conducting such a study, a simpler approach would be to assess various doses of CM (e.g., 8 vs. 10 vs. 12 g CM) on an exercise protocol that requires a predominantly aerobic energy demand and has high test-retest reliability. Furthermore, manufacturers are required to take more responsibility to guarantee that the ratio stated is what is contained within the product and researchers/practitioners should be aware of this when sourcing their product for research and/or use with athletes. Finally, those who have the resources (primarily manufacturers but also researchers) should analyze the purity of the C:M ratio to ensure they have every opportunity of achieving an ergogenic effect.
