Br J Clin Pharmacol. 2008 Jan;65(1):51- 9. Epub 2007 Jul 27
Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, B?ger RH.
Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Germany. schwedhelm@uke. uni-hamburg. de
AIMS: Oral L-arginine supplementation has been used in several studies to improve endothelium- dependent, nitric oxide (NO)-mediated vasodilation. L-Arginine treatment is hampered by extensive presystemic elimination due to intestinal arginase activity. In contrast, L-citrulline is readily absorbed and at least in part converted to L-arginine. The aim of our study was to assess this metabolic conversion and its subsequent pharmacodynamic effects. METHODS: In a double-blind, randomized, placebo-controlled cross-over study, 20 healthy volunteers received six different dosing regimes of placebo, citrulline, and arginine. Pharmacokinetic parameters (C(max), T(max), C(min), AUC) were calculated after 1 week of oral supplementation. The ratio of plasma L-arginine over asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase (arginine/ADMA ratio), urinary cyclic guanosine monophosphate (cGMP) and nitrate excretion rates, and flow-mediated
vasodilation (FMD) was measured to assess pharmacodynamic effects. RESULTS: L-Citrulline dose-dependently increased AUC and C(max) of plasma L-arginine concentration more effectively than L-arginine (P < 0.01). The highest dose of citrulline (3 g bid) increased the C(min) of plasma L-arginine and improved the L-arginine/ADMA ratio from 186 +/- 8 (baseline) to 278 +/- 14 [P < 0.01, 95% confidence interval (CI) 66, 121]. Moreover, urinary nitrate and cGMP were increased from 92 +/- 10 to 125 +/- 15 micromol mmol(-1) creatinine (P = 0.01, 95% CI 8, 58) and from 38 +/- 3.3 to 50 +/- 6.7 nmol mmol(-1) creatinine (P = 0.04, 95% CI 0.4, 24), respectively. No treatment improved FMD over baseline. However, pooled analysis of all FMD data revealed a correlation between the increase of arginine/ADMA ratio and improvement of FMD. CONCLUSION: Our data show for the first time that oral L-citrulline supplementation raises plasma L-arginine concentration and augments
NO-dependent signalling in a dose-dependent manner.
Citrulline rasied plasma arginine levels better than arginine itself. 3g/twice/day worked best.
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Thread: New Citrulline study!
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06-28-2008, 12:53 PM #1
New Citrulline study!
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06-28-2008, 01:05 PM #2
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06-28-2008, 01:15 PM #3
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06-28-2008, 01:34 PM #4
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06-28-2008, 01:41 PM #5
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06-28-2008, 02:24 PM #6
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06-28-2008, 02:36 PM #7
Would be nice. This study does add value to the growing idea of replacing arginine with citrulline for those NO Pumpalicous products though. I'd say high doses greater than 3g would be needed and in a properly designed NO formula that adds other effective ingredients (there are some good ones) there may be some nice results.
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06-28-2008, 02:40 PM #8
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06-28-2008, 02:53 PM #9
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06-28-2008, 03:19 PM #10Our data show for the first time that oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signalling in a dose-dependent manner.
.... "for the first time" ????
Knowing that oral citrulline is not subjected to degradation in the liver by Arginase I.... I can't say that I'm the least bit surprised by this study (I seriously thought this was well-known)?
Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1061-7. Epub 2007 Sep 27.
Roug? C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cocheti?re MF, Darmaun D.
UMR 1280, Physiologie des Adaptations Nutritionnelles, Centre de Recherche en Nutrition Humaine, Hotel-Dieu Hospital, Nantes Cedex 1, France.
Manipulation of citrulline availability in humans.
"Oral L-citrulline administration was associated with 1) a rise in plasma, urine, and RBC citrulline (39 +/- 4 vs. 225 +/- 44 micromol/l, 0.9 +/- 0.3 vs. 6.2 +/- 3.8 micromol/mmol creatinine, and 23 +/- 1 vs. 52 +/- 9 micromol/l, respectively); and 2) a doubling in plasma arginine level, without altering blood urea or urinary urea nitrogen excretion, and thus enhanced nitrogen balance. We conclude that 1) depletion of glutamine, the main precursor of citrulline, depletes plasma citrulline; 2) oral citrulline can be used to enhance systemic citrulline and arginine availability, because citrulline is bioavailable and very little citrulline is lost in urine; and 3) further studies are warranted to determine the mechanisms by which citrulline may enhance nitrogen balance in vivo in humans."
Curr Opin Clin Nutr Metab Care. 2007 Sep;10(5):620-6.Related Articles, Links
Curis E, Crenn P, Cynober L.
Citrulline and the gut.
"Citrulline is easily taken up by the gut, with a broad set of transporters that can remove it from the lumen in the enterocytes. This is confirmed by pharmacokinetic studies and the efficacy is so great that oral complementation with citrulline seems more efficient than complementation with arginine to provide arginine."
J Thorac Cardiovasc Surg. 2006 Jul;132(1):58-65.
Smith HA, Canter JA, Christian KG, Drinkwater DC, Scholl FG, Christman BW, Rice GD, Barr FE, Summar ML.
Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline.
"Oral citrulline supplementation safely increased plasma citrulline and arginine concentrations"~
Wherever progression lacks.... regress can be found in abundance.
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