03/24/2025
Citrulline being better than Arginine: For eliminating our shared condition of Arrhythmias (being electrical signaling problems as opposed to flow-thru or "plumbing" issues, such as Afib, tachycardias, SVT, ectopics etc), i hav used the now infamous 2006 Study (by researcher George Eby & Dr William Halcomb) in coming up with my 2018 "Core4" regimen or protocol of Taurine, Citrulline, a liquid ionic form of Magnesium and CoQ10 (Pls scroll down this page to the 2018 content to see the actual studies and the 2006 LAF conference (Lone Atrial Fibrillation Conference of 2006 session 49). I have been asked as to WHY? Citrulline, bcs the 2006 Study clearly stipulates Arginine. Thus this is what this post is about.
Introduction to study via AI Overview (AI OVERVIEW) and the studies follow this AI OVERVIEW.
QUERY: can i replace arginine with citrulline for better bioavailability
: Replacing L-arginine with L-citrulline can improve bioavailability because citrulline bypasses hepatic metabolism and is a more efficient precursor for L-arginine synthesis, leading to increased nitric oxide production.
Why L-arginine has bioavailability issues:
L-arginine undergoes significant first-pass metabolism in the liver, meaning a large portion is broken down before it can reach the systemic circulation and exert its effects.
How L-citrulline overcomes this:
L-citrulline, a non-essential amino acid, is not metabolized in the liver and can be converted to L-arginine in the kidneys.
Benefits of using L-citrulline:
Increased L-arginine availability: By bypassing liver metabolism, L-citrulline ensures a higher concentration of L-arginine in the bloodstream.
Enhanced nitric oxide production: L-arginine is a precursor to nitric oxide (NO), a molecule that plays a crucial role in vasodilation and other physiological processes.
Potential for improved exercise performance: Studies suggest that L-citrulline supplementation can improve exercise performance by enhancing blood flow and oxygen delivery to muscles.
Other potential benefits: L-citrulline has been linked to improvements in cardiovascular health, including reduced arterial stiffness and improved blood pressure.
Studies supporting L-citrulline:
Research indicates that L-citrulline supplementation can increase plasma L-arginine levels more effectively than L-arginine supplementation alone.
Studies have shown that L-citrulline can improve exercise performance and reduce fatigue.
Some studies have shown that L-citrulline supplementation can improve muscle blood flow during submaximal exercise in older men.
Considerations: While L-citrulline is generally considered safe, it's essential to consult with a healthcare professional before starting any new supplement regimen, especially if you have any underlying health conditions or are taking medications. L-citrulline might lower blood pressure, so individuals taking medications for hypertension should monitor their blood pressure closely.
Primary reference study
https://pmc.ncbi.nlm.nih.gov/articles/PMC5368575/ #:~:text=Given%20these%20drawbacks%20of%20arginine,because%20arginine%20undergoes%20increasing%20FPM.
Intro summary link quote from following study:
: Given these drawbacks of arginine supplementation, citrulline has been suggested as a potential alternative to increase arginine availability. The main support for citrulline supplementation comes from the premise that citrulline does not undergo FPM in the gut or liver (12) [although this has been questioned (13)] and that the only known fate of citrulline in vivo is its conversion to arginine (12). Furthermore, some studies have demonstrated that citrulline supplementation is as efficient as, if not more efficient than, arginine supplementation itself in increasing NO production (14, 15); however, there is a lack of quantitative data on the metabolic fate of these 2 supplements, and it is unclear which one is more efficient at increasing arginine availability. Thus, the purpose of this study was to quantify the metabolic fate of dietary arginine and citrulline supplementation under varying supplementation levels. Our hypothesis was that dietary supplementation with citrulline is more efficient than that with arginine to increase systemic arginine availability over the long term, because arginine undergoes increasing FPM.
Supporting studies and references:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7274894/ #:~:text=L-citrulline,%20a%20natural%20precursor,studies,%20along%20with%20pharmacometric%20approaches.
: L-citrulline, a natural precursor of L-arginine, is more bioavailable than L-arginine because of hepatic first-pass metabolism avoidance and longer circulation time
https://www.sciencedirect.com/science/article/pii/S2161831322004239 #:~:text=An%20approach%20to%20circumvent%20arginine%20metabolism%20is,is%20not%20a%20substrate%20for%20arginase%20(90).&text=Recent%20studies%20support%20the%20effectiveness%20of%20oral,arginine%20concentrations%20and%20NO-dependent%20signaling%20(91,%2092).
An approach to circumvent arginine metabolism is the administration of L-citrulline, which can be converted into arginine but is not a substrate for arginase
Recent studies support the effectiveness of oral L-citrulline in increasing bioavailable arginine concentrations and NO-dependent signaling
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.18070 #:~:text=Furthermore,%20L-citrulline%20has%20been,20,%2023,%2076].
Given that oral L-citrulline, a precursor and metabolite of L-arginine, bypasses gastrointestinal and liver metabolism and thus is more readily available in systemic circulation, L-citrulline may improve nitric oxide bioavailability more efficiently
https://www.sciencedirect.com/science/article/pii/S0006291X14018178 #:~:text=l-Citrulline%20is%20a%20colorless,-citrulline%20and%20l-arginine.
Furthermore, we and other researchers have demonstrated in clinical trials that l-citrulline supplementation functionally improves arterial stiffness [17], decreases the state of lipoprotein oxidation [18], reduces ankle blood pressure and carotid wave reflection [19], and causes a reduction in the heart rate-corrected QT interval as a marker of sudden cardiac death [20]. Thus, l-citrulline supplementation has been shown to exhibit several beneficial effects on the cardiovascular system.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6073798/ #:~:text=Supplemental%20l-citrulline%20increased%20l,flow%20[152,153].
Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations.
Alternatively, oral l-citrulline supplementation consistently increases plasma and tissue levels of l-arginine and NO bioavailability [10,11,12].
