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General Health & Fitness
Nutrition and Supplements
L-Citrulline Supports Vascular and Muscular Benefits of Exercise Training in Older Adults
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<blockquote data-quote="madman" data-source="post: 181475" data-attributes="member: 13851"><p><span style="color: rgb(184, 49, 47)"><strong><em>In contrast to Arg, Cit effectively bypasses the metabolism by the intestine and liver, enabling it to reach the kidneys, where it is converted to Arg [36]. These properties are desirable for increasing systemic Arg concentrations.</em></strong> </span><em>Schwedhelm et al. investigated how different dosing regiments of oral Arg and Cit affected plasma Arg concentrations (Table 1) and pharmacodynamic parameters such as plasma [Arg]/[ADMA] ratio, urinary nitrate, and cGMP excretion (a surrogate marker of NO production) and flow-mediated vasodilation (FMD) after 1 week in 20 healthy volunteers [6].</em></p><p></p><p><span style="color: rgb(184, 49, 47)"><strong><em>They found that 0.75 g of Cit given twice a day increased the Arg area under the curve (AUC) to the same extent as both 1.6 g of slow-release Arg given twice a day, and 1 g of immediate-release Arg given three times a day [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B6-nutrients-11-01679" target="_blank">6</a>], demonstrating the potency of Cit. <u>Only 1.6 g of Arg slow release twice daily and 3 g of Cit twice daily were effective to increase the plasma [Arg]/[ADMA] ratio, and only the latter regimen was successful to elevate the urinary nitrate and cGMP excretion</u>.</em></strong></span><em> None of the regiments was able to improve the FMD, and the authors suggest that this finding could be due to the short intervention duration. Interestingly, a correlation between higher FMD changes with an increased [Arg]/[ADMA] ratio was found. <strong><span style="color: rgb(44, 130, 201)"><u>The most effective regiment to elevate the [Arg]/[ADMA] ratio was 3 g of Cit twice daily, which was also the only strategy that was able to increase the urinary excretion of nitrate and cGMP</u>. These findings are consistent with this regiment also being the most effective to increase Arg AUC and thus, the total exposure of the endothelium to Arg, suggesting a correlation between plasma [Arg] and these surrogate markers of NO production.</span></strong> This correlation has also been demonstrated earlier by Bode-Böger et al. [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B28-nutrients-11-01679" target="_blank">28</a>]. The combined use of Arg and Cit has also been proposed as an alternative to the isolated use of either one. Experiments on mice and rabbits receiving oral Cit, Arg, or a combination at a half dosage of each, demonstrate that the combined use was effective at acutely raising plasma Arg levels [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B24-nutrients-11-01679" target="_blank">24</a>]. A double-blinded, randomized placebo-controlled study on 42 healthy Japanese males randomized to either oral Cit, Arg, a combination at half dosage of each, or placebo had similar results [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B43-nutrients-11-01679" target="_blank">43</a>]. A later study also found higher mean AUC 0-4 h values of plasma Arg for the simultaneous use of Arg and Cit compared to the other dosing regiments, despite not being statistically significant. Interestingly, both papers suggested that the apparent synergistic effect on short-term plasma Arg levels might be due to suppressed arginase activity caused by Cit, as demonstrated by Shearer et al. [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B44-nutrients-11-01679" target="_blank">44</a>], limiting the first-pass metabolism of Arg. The half-life of Cit has been shown to increase in dose-dependence from 0.65 to 1.14 h for dosages of 2 to 15 g [<a href="https://www.mdpi.com/2072-6643/11/7/1679/htm#B45-nutrients-11-01679" target="_blank">45</a>].</em></p><p></p><p><strong><span style="color: rgb(184, 49, 47)"><em>In summary, the evidence presented above suggests that Cit is more suited for long-term elevations of Arg levels compared to Arg on a gram-to-gram basis. </em></span></strong><em>Furthermore, the simultaneous administration of both compounds might be advantageous in situations where acute increases in plasma Arg are desired.</em></p></blockquote><p></p>
[QUOTE="madman, post: 181475, member: 13851"] [COLOR=rgb(184, 49, 47)][B][I]In contrast to Arg, Cit effectively bypasses the metabolism by the intestine and liver, enabling it to reach the kidneys, where it is converted to Arg [36]. These properties are desirable for increasing systemic Arg concentrations.[/I][/B][I] [/I][/COLOR][I]Schwedhelm et al. investigated how different dosing regiments of oral Arg and Cit affected plasma Arg concentrations (Table 1) and pharmacodynamic parameters such as plasma [Arg]/[ADMA] ratio, urinary nitrate, and cGMP excretion (a surrogate marker of NO production) and flow-mediated vasodilation (FMD) after 1 week in 20 healthy volunteers [6].[/I] [COLOR=rgb(184, 49, 47)][B][I]They found that 0.75 g of Cit given twice a day increased the Arg area under the curve (AUC) to the same extent as both 1.6 g of slow-release Arg given twice a day, and 1 g of immediate-release Arg given three times a day [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B6-nutrients-11-01679']6[/URL]], demonstrating the potency of Cit. [U]Only 1.6 g of Arg slow release twice daily and 3 g of Cit twice daily were effective to increase the plasma [Arg]/[ADMA] ratio, and only the latter regimen was successful to elevate the urinary nitrate and cGMP excretion[/U].[/I][/B][/COLOR][I] None of the regiments was able to improve the FMD, and the authors suggest that this finding could be due to the short intervention duration. Interestingly, a correlation between higher FMD changes with an increased [Arg]/[ADMA] ratio was found. [B][COLOR=rgb(44, 130, 201)][U]The most effective regiment to elevate the [Arg]/[ADMA] ratio was 3 g of Cit twice daily, which was also the only strategy that was able to increase the urinary excretion of nitrate and cGMP[/U]. These findings are consistent with this regiment also being the most effective to increase Arg AUC and thus, the total exposure of the endothelium to Arg, suggesting a correlation between plasma [Arg] and these surrogate markers of NO production.[/COLOR][/B] This correlation has also been demonstrated earlier by Bode-Böger et al. [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B28-nutrients-11-01679']28[/URL]]. The combined use of Arg and Cit has also been proposed as an alternative to the isolated use of either one. Experiments on mice and rabbits receiving oral Cit, Arg, or a combination at a half dosage of each, demonstrate that the combined use was effective at acutely raising plasma Arg levels [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B24-nutrients-11-01679']24[/URL]]. A double-blinded, randomized placebo-controlled study on 42 healthy Japanese males randomized to either oral Cit, Arg, a combination at half dosage of each, or placebo had similar results [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B43-nutrients-11-01679']43[/URL]]. A later study also found higher mean AUC 0-4 h values of plasma Arg for the simultaneous use of Arg and Cit compared to the other dosing regiments, despite not being statistically significant. Interestingly, both papers suggested that the apparent synergistic effect on short-term plasma Arg levels might be due to suppressed arginase activity caused by Cit, as demonstrated by Shearer et al. [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B44-nutrients-11-01679']44[/URL]], limiting the first-pass metabolism of Arg. The half-life of Cit has been shown to increase in dose-dependence from 0.65 to 1.14 h for dosages of 2 to 15 g [[URL='https://www.mdpi.com/2072-6643/11/7/1679/htm#B45-nutrients-11-01679']45[/URL]].[/I] [B][COLOR=rgb(184, 49, 47)][I]In summary, the evidence presented above suggests that Cit is more suited for long-term elevations of Arg levels compared to Arg on a gram-to-gram basis. [/I][/COLOR][/B][I]Furthermore, the simultaneous administration of both compounds might be advantageous in situations where acute increases in plasma Arg are desired.[/I] [/QUOTE]
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Nutrition and Supplements
L-Citrulline Supports Vascular and Muscular Benefits of Exercise Training in Older Adults
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