L-Citrulline Supports Vascular and Muscular Benefits of Exercise Training in Older Adults

[madman]

Hey Madman,

what is your dose of both L arginine and L citrulline daily? I have been taking 3 g of each together, once per day, along with 2.5 g of tadalafil prior to my workout..I do notice more vascularity when doing weights but not much else..you think the dosing is adequat? Or would the same protocol 2 times per day be better? Do you think the L arginine is needed along with the L citrulline?

regards,

Mark

Only take l-citrulline 6 grams (3 grams twice daily).

Aim for a minimum of 3 grams daily but 6 would be more effective overall.

L-arginine is not needed.




L-CIT and Vascular Function

Evidence indicates that even though oral L-ARG supplementation effectively increases L-ARG bioavailability, improvement in endothelial-mediated vasodilation is not observed in healthy middle-aged adults (20). Long-term L-ARG supplementation becomes ineffective due to increased catabolism by arginase enzyme activation (19). Alternatively, the nonessential amino acid L-CIT is better absorbed when ingested as compared with a similar dose of oral L-ARG (19). The higher circulating level of L-ARG after L-CIT ingestion is the result of lack of catabolism by arginase and hepatic uptake (19). Part of this efficiency is attributed to the ability of L-CIT to inhibit arginase activity in humans and animals (11,21). Circulating L-CIT is converted to L-ARG (de novo synthesis) and released from the kidneys into the systemic circulation (22). The greater efficacy of acute oral L-CIT as a precursor of plasma L-ARG than an equimolar dose of oral L-ARG was demonstrated by Moinard et al. (9) in older adults. We have shown increases in plasma L-ARG or NO metabolites after 1 wk (7), 2 wk (23), and 8 wk (14) of oral L-CIT in older adults. Therefore, L-CIT supplementation may have the potential to improve age-related vascular dysfunction by increasing L-ARG bioavailability for eNOS via de novo synthesis and arginase inhibition.



L-CIT combined with L-ARG may have additive effects. We found that oral supplementation with L-CIT and L-ARG caused a greater increase in plasma L-ARG, NO metabolites, and cGMP levels than the single amino acid alone in animals (21). These effects of L-CIT plus L-ARG were associated with enhanced peripheral blood flow. The upregulation of the L-ARG‐NO‐cGMP pathway by the combined amino acid supplementation was likely via the effect of L-CIT on arginase activity, acting as a strong allosteric inhibitor (19). To test for the clinical and applied utility of this combined supplementation, Suzukiet al.(35) assessed performance on a bicycle ergometer in male athletes and demonstrated that 7 d of oral L-CIT (1.2 g·d-1) and L-ARG (1.2 g·d-1) improved 10-min fullpower cycling test performance and postexercise subjective perception related to muscle fatigue. Although the L-CIT plus L-ARG combination may provide superior efficacy leading to cardiovascular benefits by promoting greater L-ARG‐NO‐cGMP bioavailability than each amino acid alone, further studies are needed to elucidate the effectiveness on exercise performance or tolerance in older adults and clinical populations. These findings suggest that L-CIT improves local muscle oxygen kinetics and cycling performance despite no changes in oxygen consumption, likely due to enhanced microvascular function and reduced ammonia accumulation. These effects may be more pronounced when combining L-CIT and L-ARG.

 

[madman]

The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure

Abstract: Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate...

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Table 1. Plasma l-arginine area under the curve (AUC) after 1 week of different l-citrulline and l-arginine dosing regiment.
View attachment 9939

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. 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].

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 [6], demonstrating the potency of Cit. 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. 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. 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. 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. This correlation has also been demonstrated earlier by Bode-Böger et al. [28]. 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 [24]. 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 [43]. 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. [44], 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 [45].

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. Furthermore, the simultaneous administration of both compounds might be advantageous in situations where acute increases in plasma Arg are desired.

 

[madman]

i have recently transitioned (see earlier post in this string) to 5mg citrulline malate (bulk powder) daily and now for 4-5 days. i haven't noticed much with pumps after lifting but i definitely noted a favorable change aerobically when running. the temperature and humidity are up this week and normally that would knock performance down but it didn't. nice! sadly, and for lack of a proper test candidate, i cant report on any erectile related changes just yet. so my go forward is now 5mg daily added to my mid-day protein shake. i may bump that up in a few weeks; dunno.

Keep in mind that you need to aim for 3 grams of L-Citrulline daily and 6 grams (3 grams twice daily) would be more effective.

Seeing as you are not using pure L-Citrulline than depending on what strength (1:1 or 2:1) of L-Citrulline DL-Malate used you will need to make sure you are taking a high enough dose to achieve 3-6 grams of L-Citrulline daily.

If you are using the 1:1 than you will need to consume 6-12 grams daily to get 3-6 grams of L-Citrulline.

If you are using the 2:1 than you will need to consume 4.5-9 grams daily to get 3-6 grams of L-Citrulline.

 

[GreenMachineX]

Do the benefits on muscle only happen if taken daily, or does it just need to be taken preworkout?

 

[DFW Guy]

Keep in mind that you need to aim for 3 grams of L-Citrulline daily and 6 grams (3 grams twice daily) would be more effective.

Seeing as you are not using pure L-Citrulline than depending on what strength (1:1 or 2:1) of L-Citrulline DL-Malate used you will need to make sure you are taking a high enough dose to achieve 3-6 grams of L-Citrulline daily.

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If you are using the 1:1 than you will need to consume 6-12 grams daily to get 3-6 grams of L-Citrulline.

If you are using the 2:1 than you will need to consume 4.5-9 grams daily to get 3-6 grams of L-Citrulline.

thank you madman for that input. since i had last posted, i had concluded the same.

i can report benefits from the lower "dose" that i am currently taking. it seems to be most evident during exercise- both jogging and lifting and quite simply my performance is up slightly at say 2%. respiration while jogging is great and even against the stifling heat and humidity we have in DFW right now. not so much with pumps or erections.

i purchased the NutraCost Citrulline Malate 2:1 with 3gms per dose. i will implement a 2nd daily dose starting today.

i will purchase straight citrulline on the next order.

finally, i will double my daily dose starting today and report back soon. but i can already advise that this is proving to be a beneficial addition.

 

[Jungle Cruiser]

FWIW - I just received an email from HR Supplements stating that Citrulline Malate is 50% off this weekend.

 

[drkelp]

I have both, arginine seems to work better for some reason, at least for me