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Erectile Dysfunction
Published in Charles Theisler, Adjuvant Medical Care, 2023
L-Citrulline: Oral citrulline supplementation raises blood arginine levels more effectively than arginine supplementation itself.7 In a single blind, short-term study of men with ED (erection hardness score of 3 out of 4), L-citrulline was given at dose of 1.5 gm/day for a month. It was concluded that citrulline was safe and psychologically well-accepted, and reported as very satisfying to the patients.8
Lysinuric protein intolerance
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Abnormal function of the urea cycle is thought to result from intramitochondrial shortage of ornithine, as in HHH syndrome (Chapter 31). In LPI, intravenous (IV) infusion of ornithine or arginine (an ornithine source) prevents the hyperammonemia of protein or alanine loading [1, 3, 11]. Infusion of citrulline also accomplishes this effect and, furthermore, it is effective orally [4, 43]. Oral arginine and ornithine are less effective because they are so poorly absorbed in this condition that supplementation leads to diarrhea [8, 44]. Citrulline is a neutral amino acid and is absorbed via a different transport system, but once in the cell, it is converted via arginine to ornithine. The nature of the defect in efflux would make for high intracellular concentration of ornithine, but the trans-stimulated system has not been found in hepatocytes [49, 50], so hepatic cells would be expected to reflect the depletion of dibasic amino acids evident in the plasma. Some clinical manifestations, such as failure to thrive, anemia, hepatomegaly, and osteoporosis, could be a function of a shortage of lysine. A further pathophysiologic link is to arginine as the starting point of creatine and NO synthesis [51].
Emerging ergogenic aids for endurance activity and weight loss
Published in Jay R Hoffman, Dietary Supplementation in Sport and Exercise, 2019
Several studies have examined the effect of citrulline supplementation on aerobic performance in humans. Suzuki et al. (71) investigated the effect of citrulline supplementation on cycling time trial performance in recreationally trained males. Subjects consumed 2.4 g citrulline per day for seven days and an additional 2.4 g one hour prior to performing a 4 km cycling time trial on day eight. Compared to a placebo, citrulline supplementation significantly reduced completion time by 1.5%, increased power output and improved subjective feelings of muscle fatigue and concentration following exercise. Bailey and colleagues (3) also demonstrated that supplementation with 6 g citrulline per day for seven days significantly improved blood pressure, increased the total amount of work completed during a cycling exercise performance test and improved exercise tolerance during high-intensity cycling in recreationally active males. Cheng et al. (18) examined the effect of administering a supplement containing 0.17 g/kg branched chain amino acids, 0.05 g/kg arginine and 0.05 g/kg citrulline one hour prior to a 5000 m and 10,000 m run time trial on two consecutive days. The supplement significantly reduced completion times in both the 5000 m and 10,000 m run in the male and female endurance runners. Citrulline supplementation may also positively contribute to endurance performance by decreasing blood lactate concentrations in response to high-intensity exercise (39, 44).
Effect of Combined Grape Seed Extract and L-Citrulline Supplementation on Hemodynamic Responses to Exercise in Young Males
Published in Journal of Dietary Supplements, 2023
Brian Shariffi, Katherine Dillon, Trevor Gillum, William Boyer, Sean Sullivan, Esther Lee, Jong-Kyung Kim
Dietary supplementation containing NO donors (such as beetroot and L-citrulline) has received attention from coaches and trainers to improve sports performance in athletes. A study previously demonstrated that dietary nitrate (NO3-) supplementation with beetroot decreased submaximal oxygen cost at the given workload during cycling exercise (11). L-citrulline supplementation increases plasma L-arginine, increasing NO and improving endothelial function, exercise performance, and lowering blood pressure (12–14). Furthermore, combined supplementation of L-arginine and L-citrulline has been shown to provide greater production of NO compared to taking either supplement alone (15). Combined supplementation also produces longer-lasting effects due to the inhibitory effects of L-citrulline on arginase, an enzyme that breaks down L-immuarginine (16,17). Despite two different pathways utilized, naturally rich substances of nitrate or L-citrulline have been identified as a good source for promoting exogenous NO production (7,18,19).
The Effects of L-Citrulline on Blood-Lactate Removal Kinetics Following Maximal-Effort Exercise
Published in Journal of Dietary Supplements, 2022
Benjamin Divito, Mackenzie McLaughlin, Ira Jacobs
While the mechanisms for L-citrulline’s actions are relatively clear and well supported, the current study’s results raise questions about the efficacy of L-citrulline for augmenting the performance of cellular systems which may likely already be maximally engaged during exercise. For example, when considering the rate of lactate disappearance from the blood (Table 2, Figures 3 and 4) it is important to recognize that lactate removal from the blood is dependent on its metabolism by metabolically active tissues throughout the body, capacities and limitations to transport, and the degree of blood flow which facilitates the transport of lactate to those metabolically active tissues. It is clear that blood vessel radius is a key determinant of peripheral blood flow, and thus a primary determinant of the degree of lactate removal from the blood should be vasodilatory control of blood vessel radius. Therefore, from a theoretical perspective, there is certainly a basis for L-citrulline or any supplement that augments in vivo nitric oxide concentration, to increase the rate of lactate disappearance from the blood. However, the results of this study suggest that the previously documented vasodilatory effects of L-citrulline ingestion may not extend to being relevant to the magnitude of physiological responses and reserves already activated and called upon in response to supramaximal intensity exercise. The results of this study suggest that there may be a physiological limit to the potential for L-citrulline supplementation to ameliorate the rate of lactate removal, the oxygen cost of exercise, and VO2peak.
Effects of Citrulline Malate Supplementation on Muscle Strength in Resistance-Trained Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Published in Journal of Dietary Supplements, 2022
Andreo F. Aguiar, Juliano Casonatto
Among NO-precursor supplements, citrulline malate (CM), a combination of citrulline (CIT) with malate in ratios ranging from 1:1 to 2:1 (Trexler et al. 2019) has received great attention from researchers in the last decade. The potential ergogenic effects of CM have been attributed to three key mechanisms. First, CIT ingestion has been shown to increase plasma L-arginine levels (Rougé et al. 2007; Sureda et al. 2010; Thibault et al. 2011). Given that L-arginine is the main substrate for synthesis of NO, it has been proposed that CM supplementation could indirectly increase NO synthesis (Pérez-Guisado and Jakeman 2010) and consequently increase blood flow and improves the supply of oxygen and energy substrates to the active muscles (Joyner and Casey 2015), thereby improving muscle performance. Second, CIT is an essential component of the urea cycle in the liver (Curis et al. 2005), where L-arginine produced from CIT is catabolized by arginase into ornithine and urea. Given that urea is the major vehicle to eliminate ammonia, a promoter of muscle fatigue (Mutch and Banister 1983), it has been suggested that CIT supplementation may improve ammonia homeostasis (Breuillard et al. 2015) and thus improving muscle function. Third, malate is an intermediate of the Krebs cycle, and its greater availability after CM supplementation could increase aerobic ATP production through anaplerotic reactions (Bendahan et al. 2002), resulting in decreased muscle fatigue and improved muscle performance (Bendahan et al. 2002; Pérez-Guisado and Jakeman 2010; Wax et al. 2016).