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Citrulline is a non-essential amino acid that is an important intermediate in the urea cycle, functioning along with Arginine and Ornithine to rid the body of ammonia, a byproduct of protein metabolism. Because Citrulline is a precursor of Arginine, it provides a readily available source material for Arginine production, which in turn, can be used for the production of Nitric Oxide (NO). NO plays a fundamental role in vascular function and blood flow. Citrulline therefore, not only supports detoxification pathways, but also supports NO production and a healthy cardiovascular system.*
L-Citrulline (Citrulline) is an important non-essential amino acid for detoxification of the liver from ammonia (waste product from oxidation), rebuilding and muscle recovery. L-Citrulline is a precursor of L- Arginine and thus plays a role in regulating Nitric Oxide (NO) production. NOW provides 750mg of L-Citrulline in a gelatin capsule.
Citrulline is found in high concentration in the liver and is not a component of any major proteins or enzymes. The amino acid citrulline is required to detoxify the liver from ammonia, which is a waste product of the body from oxidation. Citrulline promotes energy and stimulates the immune system. This
unusual amino acid is formed in the urea cycle by the addition of carbon dioxide and ammonia to L-Ornithine. It is then combined with aspartic acid to form arginosuccinic acid, which is later metabolized into the amino acid L-Arginine.
Citrulline is an amino acid that is part of the L-arginine – NO (nitric oxide) pathway. Citrulline helps to protect against shortages of arginine and can be converted to arginine. Some arginine is converted to NO, which improves arterial blood flow and relaxes blood vessels. NO also has antioxidant functions, helping to protect cardiovascular tissues from oxidative damage leading to atherosclerosis (hardening of the arteries).
Arginine is known to be involved with wound healing, removing excess ammonia from the body, protein and sperm cell synthesis and promoting the secretion of essential hormones (growth hormone, glucagon for energy, insulin for blood sugar control, etc.).
Dietary citrulline is clinically better than ornithine at supporting arginine levels and functions, even though citrulline is converted to ornithine as an intermediate step to its conversion to arginine. Arginine can also be converted back to citrulline.
NOW uses only the natural “L” form of amino acids in our products; never the synthetic “D” forms. Not all amino acids have “l” and “d” forms, so these identifying letters may not appear on the label for certain aminos. NOW Citrulline is USP (pharmaceutical grade) and produced by natural microbial fermentation.
Citrulline should not be taken at the same time as glutamine or glutamine-fortified products like some whey proteins. It can be taken at a different time of the day unless there is a severe arginine deficiency, in which case glutamine should be avoided until healthy arginine levels are restored.
Those prone to viral cold sores might find that increased intake of arginine from arginine-rich food (nuts and chocolate) or supplements may provoke new incidences. This can often be avoided by taking the amino acid l-lysine at a different time of day, typically in servings of one to three grams per day (1,000 mg = one gram). Since citrulline supports arginine levels, cold sore sufferers may want to be aware of this possible side effect from high arginine levels.
Arginine is not recommended for those who have suffered heart attacks, and anyone using medications should advise their physician before using arginine or citrulline.
“Arginine, traditionally considered to be a nutritionally dispensable (nonessential) amino acid, serves multiple functions in addition to its role in protein synthesis. It is the precursor of nitric oxide (NO), creatine, agmatine, and other polyamines, and is an intermediate in the urea cycle.”
(Lau T, et al. Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. J Clin Invest, May 2000, Volume 105, Number 9, 1217-1225)
“The conversion of plasma citrulline to arginine approximated 5.5 µmol·kg-1·hr-1 for the various groups and also was unaffected by arginine intake. Thus, endogenous arginine synthesis is not markedly responsive to acute alterations in arginine intake in healthy adults. We propose that arginine homeostasis is achieved largely via modulating arginine intake and/or the net rate of arginine degradation.”
“The physiological needs by tissues and organs for arginine are met via the endogenous synthesis of arginine and/or arginine supplied by the diet. For the U.S. population the latter amounts to about 5.4 g daily per capita.”
“Thus, part of the labeled citrulline appears to be taken up and converted to arginine at a metabolic site(s) which is separated from the plasma arginine pool and does not equilibrate with it. Subsequently, this plasma-citrulline-derived arginine is metabolized to ornithine and then to citrulline, which reappears as the 5,5-2H2 compound in plasma.”
“…ornithine oxidation is reduced in mice given an arginine-free diet. Further, our hypothesis predicts that those conditions which greatly increase the metabolic demand for arginine, such as major trauma, severe sepsis, or marked catch-up growth, would precipitate a conditional deficiency of arginine unless there was an adequate supply of arginine or citrulline available from exogenous (enteral or parenteral) sources. Also, this scheme anticipates that, in comparison with citrulline and arginine, exogenous ornithine would serve as a relatively poor substrate for maintaining body arginine balance; evidence from experimental clinical studies favors this suggestion.”
(Castillo L, et al. Plasma Arginine and Citrulline Kinetics in Adults Given Adequate and Arginine-Free Diets. Proceedings of the National Academy of Sciences, Vol 90, 7749-7753.)
“The restoration of L-arginine levels by L-citrulline but not by L-arginine was selectively blocked by L-glutamine.”
(Chakder S and Rattan S. L-Arginine Deficiency Causes Suppression of Nonadrenergic Noncholinergic Nerve-Mediated Smooth Muscle Relaxation: Role of L-Citrulline Recycling. Pharmacocoly. Vol. 282, Issue 1, 378-384, 1997)
“L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-arginine should not be recommended following acute myocardial infarction.”
(Schulman SP, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64. PMID: 16391217)
“These observations indicate that ingestion of certain NO-boosting substances, including L-arginine, L-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.”
“The oral administration of L-citrulline, as a precursor to L-arginine and NO, was reported to be beneficial in sickle cell disease in humans. Studies indicate that the L-citrulline to L-arginine recycling pathway in endothelial cells may be the principal mechanism for sustaining localized L-arginine availability for eNOS-catalyzed NO production.”
“This is consistent with the knowledge that L-citrulline is converted to L-arginine by mammalian cells, including endothelial cells. This recycling pathway might be important in sustaining the production of NO in endothelial cells, especially when L-arginine becomes limiting, as is possible in atherosclerosis. In the present study, L-citrulline produced pharmacological effects that closely resembled those of L-arginine administration and NO action. L-citrulline caused a marked improvement in endothelium-dependent vasorelaxation in response to acetylcholine, and the combination of L-citrulline and L-arginine produced a synergistic response in elevating plasma NOX and cGMP, improving rabbit ear artery blood flow and slowing the progression of atherosclerosis. A key observation was the marked up-regulation of eNOS on chronic administration of L-citrulline, and this response might explain, in part or entirely, the NO-like pharmacological effects of L-citrulline. Atherosclerosis is an inflammatory disease characterized by endothelial dysfunction and impairment of NO production.
Herein lies a plausible explanation for atherogenesis, because it is well appreciated that NO elicits a multifaceted array of pharmacological actions, all of which are protective against the progression of atherosclerosis. A common feature of inflammation and atherosclerosis is oxidative stress, which can lead not only to cell membrane injury but also the destruction of NO. Thus, the natural antioxidant properties of NO are lost, and oxidative stress continues unabated. In the present study, fatty diet-induced atherosclerosis and oxidative stress were reversed upon oral administration of L-arginine, L-citrulline, and antioxidants. These observations suggest that NO is the active species in reducing both the markers for oxidative stress and the progression of atherosclerosis.”
Hayashi T. l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13681-6. Epub 2005 Sep 12. PMID: 16157883
Disclaimer: These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.
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